Skip to main content
Log in

Inducible Nitric Oxide Synthase and Inflammatory Diseases

  • Review Article
  • Published:
Molecular Medicine Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Moncada S. (1999) Nitric oxide: discovery and impact on clinical medicine. J. R. Soc. Med. 92: 164–169.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Trowbridge HO, Emling RC. (1997) In: Inflammation: a review of the process, 5th Ed. Quintessence Pub. Co., Chicago

    Google Scholar 

  3. Wagner DA, Young VR, Tannenbaum SR. (1983) Mammalian nitrate biosynthesis: Incorporation of 15NH3 into nitrate is enhanced by endotoxin treatment. Proc. Natl. Acad. Sci. U.S.A. 80: 4518–4521.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Moncada S, Palmer RMJ, Higgs EA. (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43: 109–142.

    PubMed  CAS  Google Scholar 

  5. Stuehr DJ, Marletta MA. (1985) Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A. 82: 7738–7742.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Geller DA, Billiar TR. (1998) Molecular biology of nitric oxide synthases. Cancer Metastasis Rev. 17: 7–23.

    Article  PubMed  CAS  Google Scholar 

  7. Stuehr DJ. (1999) Mammalian nitric oxide synthases. Biochim. Biophys. Acta 1411: 217–230.

    Article  PubMed  CAS  Google Scholar 

  8. Vodovotz Y, Bogdan C, Paik J, et al. (1993) Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor β. J. Exp. Med. 178: 605–613.

    Article  PubMed  CAS  Google Scholar 

  9. Macmicking JD, Xie Qw, Nathan C. (1997) Nitric oxide and macrophage function. Annu. Rev. Immunol. 15: 323–350.

    Article  PubMed  CAS  Google Scholar 

  10. Wink DA, Feelisch M, Vodovotz Y, et al. (1999) The chemical biology of nitric oxide. In: Colton CA, Gilbert DL (eds.) Reactive Oxygen Species in Biological Systems: An Interdisciplinary approach. Kluwer Academic/Plenum Publishing, New York, pp. 245–291.

    Google Scholar 

  11. Nathan C, Xie QW. (1994) Regulation of biosynthesis of nitric oxide. J. Biol. Chem. 269: 13725–13728.

    PubMed  CAS  Google Scholar 

  12. Denninger JW, Marletta MA. (1999) Guanylate cyclase and the NO/cGMP signaling pathway. Biochim. Biophys. Acta 1411: 334–350.

    Article  PubMed  CAS  Google Scholar 

  13. Evans CH. (1995) Nitric oxide: what role does it play in inflammation and tissue destruction? Agents Actions Suppl. 47: 107–116.

    PubMed  CAS  Google Scholar 

  14. Lyons CR. (1995) The role of nitric oxide in inflammation. Adv. Immunol. 60: 323–371.

    Article  PubMed  CAS  Google Scholar 

  15. Nathan C. (1997) Inducible nitric oxide synthase: what difference does it make? J. Clin. Invest. 100: 2417–2423.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Clancy RM, Amin AR, Abramson SB. (1998) The role of nitric oxide in inflammation and immunity. Arthritis Rheum. 41: 1141–1151.

    Article  PubMed  CAS  Google Scholar 

  17. Zamora R, Billiar TR. (2000) Nitric oxide: A true inflammatory mediator. In: Mayer B (ed.) Handbook in Experimental Pharmacology. SpringerVerlag, Berlin.

    Google Scholar 

  18. Ryffel B. (1997) Impact of knockout mice in toxicology. Crit. Rev. Toxicol. 27: 135–154.

    Article  PubMed  CAS  Google Scholar 

  19. Vodovotz Y, Geiser AG, Chesler L, et al. (1996) Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor β 1 null mouse. J. Exp. Med. 183: 2337–2342.

    Article  PubMed  CAS  Google Scholar 

  20. Nathan C, Xie Qw. (1994) Nitric oxide synthases: roles, tolls, and controls. Cell 78: 915–918.

    Article  PubMed  CAS  Google Scholar 

  21. Trepicchio WL, Bozza M, Pedneault G, et al. (1996) Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J. Immunol. 157: 3627–3634.

    PubMed  CAS  Google Scholar 

  22. Bogdan C, Vodovotz Y, Paik J, et al. (1994) Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages. J. Leukoc. Biol. 55: 227–233.

    Article  PubMed  CAS  Google Scholar 

  23. Barton BE, Jackson JV. (1993) Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model. Infect. Immun. 61: 1496–1499.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Howard M, Muchamuel T, Andrade S, et al. (1993) Interleukin 10 protects mice from lethal endotoxemia. J. Exp. Med. 177: 1205–1208.

    Article  PubMed  CAS  Google Scholar 

  25. Bogdan C, Thuring H, Dlaska M, et al. (1997) Mechanism of suppression of macrophage nitric oxide release by IL-13: influence of the macrophage population. J. Immunol. 159: 4506–4513.

    PubMed  CAS  Google Scholar 

  26. Groeneveld PH, Kwappenberg KM, Langermans JA, et al. (1997) Relation between pro- and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis. Cytokine. 9: 138–142.

    Article  PubMed  CAS  Google Scholar 

  27. Billiar TR, Curran RD, Harbrecht BG, et al. (1990) Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-l-arginine inhibits endotoxin-induced nitrate/nitrate biosynthesis while promoting hepatic damage. J. Leukoc. Biol. 48: 565–569.

    Article  PubMed  CAS  Google Scholar 

  28. Cobb JP, Natanson C, Hoffman WD, et al. (1992) N omega-amino-l-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin. J. Exp. Med. 176: 1175–1182.

    Article  PubMed  CAS  Google Scholar 

  29. Vodovotz Y, Kopp JB, Takeguchi H, et al. (1998) Increased mortality, blunted production of nitric oxide, and increased production of TNF-α in endotoxemic TGF-β1 transgenic mice. J. Leukoc. Biol. 63: 31–39.

    Article  PubMed  CAS  Google Scholar 

  30. Vodovotz Y, Letterio JJ, Geiser AG, et al. (1996) Control of nitric oxide production by endogenous TGF1 and systemic nitric oxide in retinal pigment epithelial cells and peritoneal macrophages. J. Leukoc. Biol. 60: 261–270.

    Article  PubMed  CAS  Google Scholar 

  31. Perrella MA, Hsieh CM, Lee WS, et al. (1996) Arrest of endotoxin-induced hypotension by transforming growth factor β1. Proc. Natl. Acad. Sci. U.S.A. 93: 2054–2059.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Pender BS, Chen H, Ashton S, et al. (1996) Transforming growth factor β 1 alters rat peritoneal macrophage mediator production and improves survival during endotoxic shock. Eur. Cytokine Netw. 7: 137–142.

    PubMed  CAS  Google Scholar 

  33. Dimmeler S, Haendeler J, Nehls M, et al. (1997) Suppression of apoptosis by nitric oxide via inhibition of interleukin-1β-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J. Exp. Med. 185: 601–607.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Kim YM, Talanian RV, Li J, et al. (1998) Nitric oxide prevents IL-1β and IFN-γ-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1β-converting enzyme). J. Immunol. 161: 4122–4128.

    PubMed  CAS  Google Scholar 

  35. Vodovotz Y, Chesler L, Chong H, et al. (1999) Regulation of transforming growth factor β1 by nitric oxide. Cancer Res. 59: 2142–2149.

    PubMed  CAS  Google Scholar 

  36. Bonta IL, Ben-Efraim S. (1993) Involvement of inflammatory mediators in macrophage antitumor activity. J. Leukoc. Biol. 54: 613–626.

    Article  PubMed  CAS  Google Scholar 

  37. Nathan CF. (1987) Secretory products of macrophages. J. Clin. Invest. 79: 319–326.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Salvemini D, Misko TP, Masferrer JL, et al. (1993) Nitric oxide activates cyclooxygenase enzymes. Proc. Natl. Acad. Sci. U.S.A. 90: 7240–7244.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Salvemini D, Seibert K, Marino MH. (1996) PG release, as a consequence of NO-driven COX activation, contributes to the proinflammatory effects of NO. Drugs News Perspect. 4: 204–219.

    Google Scholar 

  40. Di Rosa M, Ialenti A, Ianaro A, et al. (1996) Interaction between nitric oxide and cyclo-oxygenase pathways. Prostagl. Leukotr. Essential Fatty Acids 54: 229–238.

    Article  Google Scholar 

  41. Swierkosz TA, Mitchell JA, Warner TD, et al. (1995) Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br. J. Pharmacol. 114: 1335–1342.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Corbett JA, Kwon G, Turk J, et al. (1993) IL-1 β induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric oxide. Biochemistry 32: 13767–13770.

    Article  PubMed  CAS  Google Scholar 

  43. Inoue T, Fukuo K, Morimoto S, et al. (1993) Nitric oxide mediates interleukin-1-induced prostaglandin E2 production by vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 194: 420–424.

    Article  PubMed  CAS  Google Scholar 

  44. Zamora R, Bult H, Herman AG. (1998) The role of prostaglandin E2 and nitric oxide in cell death in J774 murine macrophages. Eur. J. Pharmacol. 349: 307–315.

    Article  PubMed  CAS  Google Scholar 

  45. Hughes FJ, Buttery LK, Hukkanen MJ, et al. (1999) Cytokine-induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and independent mechanism in rat osteoblasts in vitro. J. Biol. Chem. 274: 1776–1782.

    Article  PubMed  CAS  Google Scholar 

  46. Stadler J, Harbrecht BG, Di Silvio M, et al. (1993) Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells. J. Leukoc. Biol. 53: 165–172.

    Article  PubMed  CAS  Google Scholar 

  47. Stadler J, Stefanovic-Racic M, Billiar TR, et al. (1991) Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J. Immunol. 147: 3915–3920.

    PubMed  CAS  Google Scholar 

  48. Kosonen O, Kankaanranta H, Malo-Ranta U, et al. (1998) Inhibition by nitric oxide-releasing compounds of prostacyclin production in human endothelial cells. Br. J. Pharmacol. 125: 247–254.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Marotta P, Sautebin L, Di Rosa M. (1992) Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. Br. J. Pharmacol. 107: 640–641.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Bulut V, Severn A, Liew FY. (1993) Nitric oxide production by murine macrophages is inhibited by prolonged elevation of cyclic AMP. Biochem. Biophys. Res. Commun. 195: 1134–1138.

    Article  PubMed  CAS  Google Scholar 

  51. Milano S, Arcoleo F, Dieli M, et al. (1995) Prostaglandin E2 regulates inducible nitric oxide synthase in the murine macrophage cell line J774. Prostaglandins 49: 105–115.

    Article  PubMed  CAS  Google Scholar 

  52. Pang L, Hoult JRS. (1996) Induction of cyclooxygenase and nitric oxide synthase in endotoxin-activated J774 macrophages is differentially regulated by indomethacin: Enhanced cyclooxygenase-2 protein expression but reduction of inducible nitric oxde synthase. Eur. J. Pharmacol. 317: 151–155.

    Article  PubMed  CAS  Google Scholar 

  53. Brouet I, Ohshima H. (1995) Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem. Biophys. Res. Commun. 206: 533–540.

    Article  PubMed  CAS  Google Scholar 

  54. Kepka-Lenhart D, Chen L-C, Morris SM. (1996) Novel actions of aspirin and sodium salicylate: discordant effects on nitric oxide synthesis and induction of nitric oxide synthase mRNA in a murine macrophage cell line. J. Leukoc. Biol. 59: 840–846.

    Article  PubMed  CAS  Google Scholar 

  55. Sanchez dM, de Frutos T, Gonzalez-Fernandez F, et al. (1999) Aspirin inhibits inducible nitric oxide synthase expression and tumour necrosis factor-alpha release by cultured smooth muscle cells. Eur. J. Clin. Invest 29: 93–99.

    Article  Google Scholar 

  56. Harbrecht BG, Kim YM, Wirant EA, et al. (1997) Timing of prostaglandin exposure is critical for the inhibition of LPS- or IFN-γ-induced macrophage NO synthesis by PGE2. J. Leukoc. Biol. 61: 712–720.

    Article  PubMed  CAS  Google Scholar 

  57. Moncada S. (1997) Nitric oxide in the vasculature: physiology and pathophysiology. Ann. N. Y. Acad. Sci. 811: 60–67.

    Article  PubMed  CAS  Google Scholar 

  58. Cuzzocrea S, Zingarelli B, Hake P, et al. (1998) Antiinflammatory effects of mercaptoethyl-guanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. Free Radic. Biol. Med. 24: 450–459.

    Article  PubMed  CAS  Google Scholar 

  59. Salvemini D, Wang ZQ, Bourdon DM, et al. (1996) Evidence of peroxynitrite involvement in the carrageenan-induced rat paw edema. Eur. J. Pharmacol. 303: 217–220.

    Article  PubMed  CAS  Google Scholar 

  60. Salvemini D, Wang ZQ, Wyatt PS, et al. (1996) Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br. J. Pharmacol. 118: 829–838.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Handy RL, Moore PK. (1998) A comparison of the effects of l-NAME, 7-NI and l-NIL on carrageenan-induced hindpaw oedema and NOS activity. Br. J. Pharmacol. 123: 1119–1126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Cuzzocrea S, Sautebin L, De Sarro G, et al. (1999) Role of IL-6 in the pleurisy and lung injury caused by carrageenan. J. Immunol. 163: 5094–5104.

    PubMed  CAS  Google Scholar 

  63. Ridger VC, Pettipher ER, Bryant CE, et al. (1997) Effect of the inducible nitric oxide synthase inhibitors aminoguanidine and l-N6-(1-iminoethyl)lysine on zymosan-induced plasma extravasation in rat skin. J. Immunol. 159: 383–390.

    PubMed  CAS  Google Scholar 

  64. Vergnolle N, Hollenberg MD, Sharkey KA, et al. (1999) Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw. Br. J. Pharmacol. 127: 1083–1090.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Wang R, Ghahary A, Shen YJ, et al. (1996) Human dermal fibroblasts produce nitric oxide and express both constitutive and inducible nitric oxide synthase isoforms. J. Invest. Dermatol. 106: 419–427.

    Article  PubMed  CAS  Google Scholar 

  66. Kubes P, Suzuki M, Granger DN. (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. U.S.A. 88: 4651–4655.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Spiecker M, Peng HB, Liao JK. (1997) Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IκBα. J. Biol. Chem. 272: 30969–30974.

    Article  PubMed  CAS  Google Scholar 

  68. Peng HB, Spiecker M, Liao JK. (1998) Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation. J. Immunol. 161: 1970–1976.

    PubMed  CAS  Google Scholar 

  69. Hickey MJ, Sharkey KA, Sihota EG, et al. (1997) Inducible nitric oxide synthase-deficient mice have enhanced leukocyte-endothelium interactions in endotoxemia. FASEB J. 11: 955–964.

    Article  PubMed  CAS  Google Scholar 

  70. Macmicking JD, Nathan C, Hom G, et al. (1995) Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81: 641–650.

    Article  PubMed  CAS  Google Scholar 

  71. Cockrell A, Laroux FS, Jourd’heuil D, et al. (1999) Role of inducible nitric oxide synthase in leukocyte extravasation in vivo. Biochem. Biophys. Res. Commun. 257: 684–686.

    Article  PubMed  CAS  Google Scholar 

  72. Szabo C. (1998) Role of poly(ADP-ribose)-synthetase in inflammation. Eur. J. Pharmacol. 350: 1–19.

    Article  PubMed  CAS  Google Scholar 

  73. Szabo C, Dawson VL. (1998) Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion. Trends. Pharmacol. Sci. 19: 287–298.

    Article  PubMed  CAS  Google Scholar 

  74. Cuzzocrea S, Costantino G, Zingarelli B, et al. (1999) Protective effects of poly (ADP-ribose) synthase inhibitors in zymosan-activated plasma induced paw edema. Life Sci. 65: 957–964.

    Article  PubMed  CAS  Google Scholar 

  75. Szabo C, Lim LH, Cuzzocrea S, et al. (1997) Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J. Exp. Med. 186: 1041–1049.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Glauser MP, Zanetti G, Baumgartner JD, et al. (1991) Septic shock: pathogenesis. Lancet 338: 732–736.

    Article  PubMed  CAS  Google Scholar 

  77. Parrillo JE. (1993) Pathogenetic mechanisms of septic shock. N. Engl. J. Med. 328: 1471–1477.

    Article  PubMed  CAS  Google Scholar 

  78. Kilbourn RG, Gross SS, Jubran A, et al. (1990) NG-methyl-l-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc. Natl. Acad. Sci. U.S.A. 87: 3629–3632.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Petros A, Bennett D, Vallance P. (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338: 1557–1558.

    Article  PubMed  CAS  Google Scholar 

  80. Liu S, Adcock IM, Old RW, et al. (1993) Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA. Biochem. Biophys. Res. Commun. 196: 1208–1213.

    Article  PubMed  CAS  Google Scholar 

  81. Symeonides S, Balk RA. (1999) Nitric oxide in the pathogenesis of sepsis. Infect. Dis. Clin. North Am. 13: 449–463.

    Article  PubMed  CAS  Google Scholar 

  82. Wolkow PP. (1998) Involvement and dual effects of nitric oxide in septic shock. Inflamm. Res. 47: 152–166.

    Article  PubMed  CAS  Google Scholar 

  83. Nussler AK, Billiar TR. (1993) Inflammation, immunoregulation, and inducible nitric oxide synthase. J. Leukoc. Biol. 54: 171–178.

    Article  PubMed  CAS  Google Scholar 

  84. Szabo C, Southan GJ, Thiemermann C. (1994) Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase. Proc. Natl. Acad. Sci. U.S.A. 91: 12472–12476.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Wu CC, Chen SJ, Szabo C, et al. (1995) Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. Br. J. Pharmacol. 114: 1666–1672.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Harbrecht BG, Billiar TR, Stadler J, et al. (1992) Inhibition of nitric oxide synthesis during endotoxemia promotes intrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J. Leukoc. Biol. 52: 390–394.

    Article  PubMed  CAS  Google Scholar 

  87. Harbrecht BG, Stadler J, Demetris AJ, et al. (1994) Nitric oxide and prostaglandins interact to prevent hepatic damage during murine endotoxemia. Am. J. Physiol. 266: G1004–G1010.

    PubMed  CAS  Google Scholar 

  88. Ou J, Carlos TM, Watkins SC, et al. (1997) Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia. Nitric. Oxide. 1: 404–416.

    Article  PubMed  CAS  Google Scholar 

  89. Liaudet L, Rosselet A, Schaller MD, et al. (1998) Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock. J. Infect. Dis. 177: 127–132.

    Article  PubMed  CAS  Google Scholar 

  90. Vos TA, Gouw AS, Klok PA, et al. (1997) Differential effects of nitric oxide synthase inhibitors on endotoxin-induced liver damage in rats. Gastroenterology 113: 1323–1333.

    Article  PubMed  CAS  Google Scholar 

  91. Wink DA, Feelisch M, Fukuto J, et al. (1998) The cytotoxicity of nitroxyl: possible implications for the pathophysiological role of NO. Arch. Biochem. Biophys. 351: 66–74.

    Article  PubMed  CAS  Google Scholar 

  92. Frank S, Zacharowski K, Wray GM, et al. (1999) Identification of copper/zinc superoxide dismutase as a novel nitric oxide-regulated gene in rat glomerular mesangial cells and kidneys of endotoxemic rats. FASEB J. 13: 869–882.

    Article  PubMed  CAS  Google Scholar 

  93. Wei XQ, Charles IG, Smith A, et al. (1995) Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375: 408–411.

    Article  PubMed  CAS  Google Scholar 

  94. Laubach VE, Shesely EG, Smithies O, et al. (1995) Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc. Natl. Acad. Sci. U.S.A. 92: 10688–10692.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Nicholson SC, Grobmyer SR, Shiloh MU, et al. (1999) Lethality of endotoxin in mice genetically deficient in the respiratory burst oxidase, inducible nitric oxide synthase, or both. Shock 11: 253–258.

    Article  PubMed  CAS  Google Scholar 

  96. Cobb JP, Hotchkiss RS, Swanson PE, et al. (1999) Inducible nitric oxide synthase gene deficiency increases the mortality of sepsis in mice. Surgery 126: 438–442.

    Article  PubMed  CAS  Google Scholar 

  97. Sriskandan S, Cohen J. (1995) The pathogenesis of septic shock. J. Infect. 30: 201–206.

    Article  PubMed  CAS  Google Scholar 

  98. Li J, Billiar TR. (1999) Determinants of Nitric Oxide Protection and Toxicity in Liver. Am. J. Physiol. 276: G1069–G1073.

    Article  PubMed  CAS  Google Scholar 

  99. Kim YM, Bombeck CA, Billiar TR. (1999) Nitric oxide as a bifunctional regulator of apoptosis. Circ. Res. 84: 253–256.

    Article  PubMed  CAS  Google Scholar 

  100. Fukatsu K, Saito H, Fukushima R, et al. (1995) Detrimental effects of a nitric oxide synthase inhibitor (N-omega-nitro-l-arginine-methylester) in a murine sepsis model. Arch. Surg. 130: 410–414.

    Article  PubMed  CAS  Google Scholar 

  101. Park JH, Chang SH, Lee KM, et al. (1996) Protective effect of nitric oxide in an endotoxin-induced septic shock. Am. J. Surg. 171: 340–345.

    Article  PubMed  CAS  Google Scholar 

  102. Hierholzer C, Harbrecht B, Menezes JM, et al. (1998) Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock. J. Exp. Med. 187: 917–928.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Szabo C, Billiar TR. (1999) Novel roles of nitric oxide in hemorrhagic shock. Shock 12: 1–9.

    Article  PubMed  CAS  Google Scholar 

  104. Xie Qw, Kashiwabara Y, Nathan C. (1994) Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J. Biol. Chem. 269: 4705–4708.

    PubMed  CAS  Google Scholar 

  105. Spink J, Cohen J, Evans TJ. (1995) The cytokine responsive vascular smooth muscle cell enhancer of inducible nitric oxide synthase. Activation by nuclear factor-kappa B. J. Biol. Chem. 270: 29541–29547.

    Article  PubMed  CAS  Google Scholar 

  106. Wong HR, Finder JD, Wasserloos K, et al. (1996) Transcriptional regulation of iNOS by IL-1 β in cultured rat pulmonary artery smooth muscle cells. Am. J. Physiol. 271: L166–L171.

    PubMed  CAS  Google Scholar 

  107. Taylor BS, de Vera ME, Ganster RW, et al. (1998) Multiple NF-kappa B enhancer elements regulate cytokine induction of the human inducible nitric oxide synthase gene. J. Biol. Chem. 273: 15148–15156.

    Article  PubMed  CAS  Google Scholar 

  108. Liu SF, Ye X, Malik AB. (1997) In vivo inhibition of nuclear factor-kappa B activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock. J. Immunol. 159: 3976–3983.

    PubMed  CAS  Google Scholar 

  109. Oliver FJ, Menissier-de Murcia J, Nacci C, et al. (1999) Resistance to endotoxic shock as a consequence of defective NF-kappa B activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J. 18: 4446–4454.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Abbas AK, Murphy KM, Sher A. (1996) Functional diversity of helper T lymphocytes. Nature 383: 787–793.

    Article  PubMed  CAS  Google Scholar 

  111. Mosmann TR, Sad S. (1996) The expanding universe of T-cell subsets: Th1, Th2 and more [see comments]. Immunol. Today 17: 138–146.

    Article  PubMed  CAS  Google Scholar 

  112. Kroncke KD, Fehsel K, Kolb-Bachofen V. (1998) Inducible nitric oxide synthase in human diseases. Clin. Exp. Immunol. 113: 147–156.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Kolb H, Kolb-Bachofen V. (1998) Nitric oxide in autoimmune disease: cytotoxic or regulatory mediator? Immunol. Today 19: 556–561.

    Article  PubMed  CAS  Google Scholar 

  114. Efron DT, Kirk SJ, Regan MC, et al. (1991) Nitric oxide generation from l-arginine is required for optimal human peripheral blood lymphocyte DNA synthesis. Surgery 110: 327–334.

    PubMed  CAS  Google Scholar 

  115. Shoker AS, Yang H, Murabit MA, et al. (1997) Analysis of the in vitro effect of exogenous nitric oxide on human lymphocytes. Mol. Cell Biochem. 171: 75–83.

    Article  PubMed  CAS  Google Scholar 

  116. Schuberth HJ, Hendricks A, Leibold W. (1998) There is no regulatory role for induced nitric oxide in the regulation of the in vitro proliferative response of bovine mononuclear cells to mitogens, alloantigens or superantigens. Immunobiology 198: 439–450.

    Article  PubMed  CAS  Google Scholar 

  117. Taylor-Robinson AW. (1997) Counter-regulation of T helper 1 cell proliferation by nitric oxide and interleukin-2. Biochem. Biophys. Res. Commun. 233: 14–19.

    Article  PubMed  CAS  Google Scholar 

  118. Chang RH, Feng MH, Liu WH, et al. (1997) Nitric oxide increased interleukin-4 expression in T lymphocytes. Immunology 90: 364–369.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Bauer H, Jung T, Tsikas D, et al. (1997) Nitric oxide inhibits the secretion of T-helper 1- and T-helper 2-associated cytokines in activated human T cells. Immunology 90: 205–211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Sanders SP. (1999) Nitric oxide in asthma. Pathogenic, therapeutic, or diagnostic? Am. J. Respir. Cell Mol. Biol. 21: 147–149.

    Article  PubMed  CAS  Google Scholar 

  121. Kosonen O, Kankaanranta H, Lahde M, et al. (1998) Nitric oxide-releasing oxatriazole derivatives inhibit human lymphocyte proliferation by a cyclic GMP-independent mechanism. J. Pharmacol. Exp. Ther. 286: 215–220.

    PubMed  CAS  Google Scholar 

  122. Bingisser RM, Tilbrook PA, Holt PG, et al. (1998) Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J. Immunol. 160: 5729–5734.

    PubMed  CAS  Google Scholar 

  123. Gold DP, Schroder K, Powell HC, et al. (1997) Nitric oxide and the immunomodulation of experimental allergic encephalomyelitis. Eur. J. Immunol. 27: 2863–2869.

    Article  PubMed  CAS  Google Scholar 

  124. McCartney-Francis N, Allen JB, Mizel DE, et al. (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J. Exp. Med. 178: 749–754.

    Article  PubMed  CAS  Google Scholar 

  125. Fletcher DS, Widmer WR, Luell S, et al. (1998) Therapeutic administration of a selective inhibitor of nitric oxide synthase does not ameliorate the chronic inflammation and tissue damage associated with adjuvant-induced arthritis in rats. J. Pharmacol. Exp. Ther. 284: 714–721.

    PubMed  CAS  Google Scholar 

  126. McInnes IB, Leung B, Wei XQ, et al. (1998) Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase. J. Immunol. 160: 308–315.

    PubMed  CAS  Google Scholar 

  127. Cross AH, Misko TP, Lin RF, et al. (1994) Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice. J. Clin. Invest. 93: 2684–2690.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Zhao W, Tilton RG, Corbett JA, et al. (1996) Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase. J. Neuroimmunol. 64: 123–133.

    Article  PubMed  CAS  Google Scholar 

  129. Brenner T, Brocke S, Szafer F, et al. (1997) Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. J. Immunol. 158: 2940–2946.

    PubMed  CAS  Google Scholar 

  130. Zielasek J, Jung S, Gold R, et al. (1995) Administration of nitric oxide synthase inhibitors in experimental autoimmune neuritis and experimental autoimmune encephalomyelitis. J. Neuroimmunol. 58: 81–88.

    Article  PubMed  CAS  Google Scholar 

  131. Shin T, Tanuma N, Kim S, et al. (1998) An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats. J. Neuroimmunol. 92: 133–138.

    Article  PubMed  CAS  Google Scholar 

  132. Gabbai FB, Boggiano C, Peter T, et al. (1997) Inhibition of inducible nitric oxide synthase intensifies injury and functional deterioration in autoimmune interstitial nephritis. J. Immunol. 159: 6266–6275.

    PubMed  CAS  Google Scholar 

  133. Hoey S, Grabowski PS, Ralston SH, et al. (1997) Nitric oxide accelerates the onset and increases the severity of experimental autoimmune uveoretinitis through an IFN-gamma-dependent mechanism. J. Immunol. 159: 5132–5142.

    PubMed  CAS  Google Scholar 

  134. Tarrant TK, Silver PB, Wahlsten JL, et al. (1999) Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis. J. Exp. Med. 189: 219–230.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Fenyk-Melody JE, Garrison AE, Brunnert SR, et al. (1998) Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene. J. Immunol. 160: 2940–2946.

    PubMed  CAS  Google Scholar 

  136. Ding M, Zhang M, Wong JL, et al. (1998) Antisense knockdown of inducible nitric oxide synthase inhibits induction of experimental autoimmune encephalomyelitis in SJL/J mice. J. Immunol. 160: 2560–2564.

    PubMed  CAS  Google Scholar 

  137. Xiong Y, Karupiah G, Hogan SP, et al. (1999) Inhibition of allergic airway inflammation in mice lacking nitric oxide synthase 2. J. Immunol. 162: 445–452.

    PubMed  CAS  Google Scholar 

  138. Gilkeson GS, Mudgett JS, Seldin MF, et al. (1997) Clinical and serologic manifestations of autoimmune disease in MRl-lpr/lpr mice lacking nitric oxide synthase type 2. J. Exp. Med. 186: 365–373.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Cattell V, Cook HT, Ebrahim H, et al. (1998) Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2. Kidney Int. 53: 932–936.

    Article  PubMed  CAS  Google Scholar 

  140. Langrehr JM, Hoffman RA, Lancaster JRJ, et al. (1993) Nitric oxide — a new endogenous immunomodulator. Transplantation 55: 1205–1212.

    Article  PubMed  CAS  Google Scholar 

  141. Billiar TR. (1995) Nitric oxide. Novel biology with clinical relevance. Ann. Surg. 221: 339–349.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Hoffman RA, Langrehr JM, Berry LM, et al. (1996) Bystander injury of host lymphoid tissue during murine graft-versus-host disease is mediated by nitric oxide. Transplantation 61: 610–618.

    Article  PubMed  CAS  Google Scholar 

  143. Falzarano G, Krenger W, Snyder KM, et al. (1996) Suppression of B-cell proliferation to lipopolysaccharide is mediated through induction of the nitric oxide pathway by tumor necrosis factor in mice with acute graft-versus-host disease. Blood 87: 2853–2860.

    Article  PubMed  CAS  Google Scholar 

  144. Bobe P, Benihoud K, Grandjon D, et al. (1999) Nitric oxide mediation of active immunosup-pression associated with graft-versus-host reaction. Blood 94: 1028–1037.

    Article  PubMed  CAS  Google Scholar 

  145. Hoffman RA, Nussler NC, Gleixner SL, et al. (1997) Attenuation of lethal graft-versus-host disease by inhibition of nitric oxide synthase. Transplantation 63: 94–100.

    Article  PubMed  CAS  Google Scholar 

  146. Bastian NR, Xu S, Shao XL, et al. (1994) N-omega-monomethyl-l-arginine inhibits nitric oxide production in murine cardiac allografts but does not affect graft rejection. Biochim. Biophys. Acta 1226: 225–231.

    Article  PubMed  CAS  Google Scholar 

  147. Winlaw DS, Schyvens CG, Smythe GA, et al. (1995) Selective inhibition of nitric oxide production during cardiac allograft rejection causes a small increase in graft survival. Transplantation 60: 77–82.

    Article  PubMed  CAS  Google Scholar 

  148. Goto M, Yamaguchi Y, Ichiguchi O, et al. (1997) Phenotype and localization of macrophages expressing inducible nitric oxide synthase in rat hepatic allograft rejection. Transplantation 64: 303–310.

    Article  PubMed  CAS  Google Scholar 

  149. Tanaka S, Kamiike W, Ito T, et al. (1995) Generation of nitric oxide as a rejection marker in rat pancreas transplantation. Transplantation 60: 713–717.

    Article  PubMed  CAS  Google Scholar 

  150. McDermott CD, Gavita SM, Shennib H, et al. (1997) Immunohistochemical localization of nitric oxide synthase and the oxidant peroxynitrite in lung transplant recipients with obliterative bronchiolitis. Transplantation 64: 270–274.

    Article  PubMed  CAS  Google Scholar 

  151. Lafond-Walker A, Chen CL, Augustine S, et al. (1997) Inducible nitric oxide synthase expression in coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis. Am. J. Pathol. 151: 919–925.

    PubMed  PubMed Central  CAS  Google Scholar 

  152. Shears LL, Kawaharada N, Tzeng E, et al. (1997) Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis. J. Clin. Invest. 100: 2035–2042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Szabolcs MJ, Ravalli S, Minanov O, et al. (1998) Apoptosis and increased expression of inducible nitric oxide synthase in human allograft rejection. Transplantation 65: 804–812.

    Article  PubMed  CAS  Google Scholar 

  154. Watkins SC, Macaulay W, Turner D, et al. (1997) Identification of inducible nitric oxide synthase in human macrophages surrounding loosened hip prostheses. Am. J. Pathol. 150: 1199–1206.

    PubMed  PubMed Central  CAS  Google Scholar 

  155. Samlowski WE, Yim CY, McGregor JR. (1998) Nitric oxide exposure inhibits induction of lymphokine-activated killer cells by inducing precursor apoptosis. Nitric. Oxide. 2: 45–56.

    Article  PubMed  CAS  Google Scholar 

  156. Pou S, Pou WS, Bredt DS, et al. (1992) Generation of superoxide by purified brain nitric oxide synthase. J. Biol. Chem. 267: 24173–24176.

    PubMed  CAS  Google Scholar 

  157. Wink DA, Hanbauer I, Grisham MB, et al. (1996) Chemical biology of nitric oxide: regulation and protective and toxic mechanisms. Curr. Top. Cell Regul. 34: 159–187.

    Article  PubMed  CAS  Google Scholar 

  158. Beckman JS, Koppenol WH. (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol. 271: C1424–C1437.

    Article  PubMed  CAS  Google Scholar 

  159. Mayer B, Hemmens B. (1997) Biosynthesis and action of nitric oxide in mammalian cells [published erratum appears in Trends Biochem. Sci. 1998, 23:87]. Trends. Biochem. Sci. 22: 477–481.

    Article  PubMed  CAS  Google Scholar 

  160. Halliwell B. (1997) What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett. 411: 157–160.

    Article  PubMed  CAS  Google Scholar 

  161. Wizemann TM, Gardner CR, Laskin JD, et al. (1994) Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia. J. Leukoc. Biol. 56: 759–768.

    Article  PubMed  CAS  Google Scholar 

  162. Szabo C, Salzman AL, Ischiropoulos H. (1995) Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo. FEBS Lett. 363: 235–238.

    Article  PubMed  CAS  Google Scholar 

  163. Kamisaki Y, Wada K, Ataka M, et al. (1997) Lipopolysaccharide-induced increase in plasma nitrotyrosine concentrations in rats. Biochim. Biophys. Acta 1362: 24–28.

    Article  PubMed  CAS  Google Scholar 

  164. Numata M, Suzuki S, Miyazawa N, et al. (1998) Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs. J. Immunol. 160: 3031–3037.

    PubMed  CAS  Google Scholar 

  165. Cuzzocrea S, Zingarelli B, Costantino G, et al. (1999) Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in carrageenan-induced pleurisy. Free Radic. Biol. Med. 26: 25–33.

    Article  PubMed  CAS  Google Scholar 

  166. Miller MJ, Thompson JH, Zhang XJ, et al. (1995) Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 109: 1475–1483.

    Article  PubMed  CAS  Google Scholar 

  167. Sadowska-Krowicka H, Mannick EE, Oliver PD, et al. (1998) Genistein and gut inflammation: role of nitric oxide. Proc. Soc. Exp. Biol. Med. 217: 351–357.

    Article  PubMed  CAS  Google Scholar 

  168. van der Veen RC, Hinton DR, Incardonna F, et al. (1997) Extensive peroxynitrite activity during progressive stages of central nervous system inflammation. J. Neuroimmunol. 77: 1–7.

    Article  PubMed  Google Scholar 

  169. Cross AH, Manning PT, Stern MK, et al. (1997) Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J. Neuroimmunol. 80: 121–130.

    Article  PubMed  CAS  Google Scholar 

  170. Liu P, Hock CE, Nagele R, et al. (1997) Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. Am. J. Physiol. 272: H2327–H2336.

    Article  PubMed  CAS  Google Scholar 

  171. Liu P, Yin K, Nagele R, et al. (1998) Inhibition of nitric oxide synthase attenuates peroxynitrite generation, but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats. J. Pharmacol. Exp. Ther. 284: 1139–1146.

    PubMed  CAS  Google Scholar 

  172. Oyama J, Shimokawa H, Momii H, et al. (1998) Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo. J. Clin. Invest. 101: 2207–2214.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Heeringa P, van Goor H, Moshage H, et al. (1998) Expression of iNOS, eNOS, and peroxynitrite-modified proteins in experimental anti-myeloperoxidase associated crescentic glomerulonephritis. Kidney Int. 53: 382–393.

    Article  PubMed  CAS  Google Scholar 

  174. Beckmann JS, Ye YZ, Anderson PG, et al. (1994) Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol. Chem. Hoppe Seyler 375: 81–88.

    Article  PubMed  CAS  Google Scholar 

  175. Luoma JS, Stralin P, Marklund SL, et al. (1998) Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. Arterioscler. Thromb. Vasc. Biol. 18: 157–167.

    Article  PubMed  CAS  Google Scholar 

  176. Kooy NW, Royall JA, Ye YZ, et al. (1995) Evidence for in vivo peroxynitrite production in human acute lung injury. Am. J. Respir. Crit. Care Med. 151: 1250–1254.

    PubMed  CAS  Google Scholar 

  177. Saleh D, Ernst P, Lim S, et al. (1998) Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid. FASEB J. 12: 929–937.

    Article  PubMed  CAS  Google Scholar 

  178. Bagasra O, Michaels FH, Zheng YM, et al. (1995) Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 92: 12041–12045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Cross AH, Manning PT, Keeling RM, et al. (1998) Peroxynitrite formation within the central nervous system in active multiple sclerosis. J. Neuroimmunol. 88: 45–56.

    Article  PubMed  CAS  Google Scholar 

  180. Kooy NW, Lewis SJ, Royall JA, et al. (1997) Extensive tyrosine nitration in human myocardial inflammation: evidence for the presence of peroxynitrite. Crit. Care Med. 25: 812–819.

    Article  PubMed  CAS  Google Scholar 

  181. Wink DA, Cook JA, Kim SY, et al. (1997) Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates. Chemical aspects involved in the balance between oxidative and nitrosative stress. J. Biol. Chem. 272: 11147–11151.

    Article  PubMed  CAS  Google Scholar 

  182. Beckman JS. (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem. Res. Toxicol. 9: 836–844.

    Article  PubMed  CAS  Google Scholar 

  183. van d, V, Eiserich JP, Halliwell B, et al. (1997) Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite. A potential additional mechanism of nitric oxide-dependent toxicity. J. Biol. Chem. 272: 7617–7625.

    Article  Google Scholar 

  184. Hazen SL, Zhang R, Shen Z, et al. (1999) Formation of nitric oxide-derived oxidants by myeloperoxidase in monocytes: pathways for monocyte-mediated protein nitration and lipid peroxidation In vivo. Circ. Res. 85: 950–958.

    Article  PubMed  CAS  Google Scholar 

  185. Wu W, Chen Y, Hazen SL. (1999) Eosinophil peroxidase nitrates protein tyrosyl residues. Implications for oxidative damage by nitrating intermediates in eosinophilic inflammatory disorders. J. Biol. Chem. 274: 25933–25944.

    Article  PubMed  CAS  Google Scholar 

  186. Studer R, Jaffurs D, Stefanovic-Racic M et al. (1999) Nitric oxide in osteoarthritis. Osteoarthritis Cartilage. 7: 377–379.

    Article  PubMed  CAS  Google Scholar 

  187. Lotz M. (1999) The role of nitric oxide in articular cartilage damage. Rheum. Dis. Clin. North Am. 25: 269–282.

    Article  PubMed  CAS  Google Scholar 

  188. Olee T, Hashimoto S, Quach J, et al. (1999) IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J. Immunol. 162: 1096–1100.

    PubMed  CAS  Google Scholar 

  189. Oates JC, Ruiz P, Alexander A, et al. (1997) Effect of late modulation of nitric oxide production on murine lupus. Clin. Immunol. Immunopathol. 83: 86–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Santos LL, Morand EF, Yang Y, et al. (1997) Suppression of adjuvant arthritis and synovial macrophage inducible nitric oxide by N-iminoethyl-l-ornithine, a nitric oxide synthase inhibitor. Inflammation 21: 299–311.

    Article  PubMed  CAS  Google Scholar 

  191. Stefanovic-Racic M, Meyers K, Meschter C, et al. (1994) N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis Rheum. 37: 1062–1069.

    Article  PubMed  CAS  Google Scholar 

  192. McCartney-Francis NL, Song XY, Mizel DE, et al. (1999) Hemoglobin protects from streptococcal cell wall-induced arthritis. Arthritis Rheum. 42: 1119–1127.

    Article  PubMed  CAS  Google Scholar 

  193. Lubberts E, Joosten LA, van Den BL, et al. (1999) Adenoviral vector-mediated overexpression of IL-4 in the knee joint of mice with collagen-induced arthritis prevents cartilage destruction. J. Immunol. 163: 4546–4556.

    PubMed  CAS  Google Scholar 

  194. Miesel R, Kurpisz M, Kroger H. (1996) Suppression of inflammatory arthritis by simultaneous inhibition of nitric oxide synthase and NADPH oxidase. Free Radic. Biol. Med. 20: 75–81.

    Article  PubMed  CAS  Google Scholar 

  195. Gassner R, Buckley MJ, Georgescu H, et al. (1999) Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase. J. Immunol. 163: 2187–2192.

    PubMed  CAS  Google Scholar 

  196. Borderie D, Hilliquin P, Hernvann A, et al. (1999) Apoptosis induced by nitric oxide is associated with nuclear p53 protein expression in cultured osteoarthritic synoviocytes. Osteoarthritis. Cartilage. 7: 203–213.

    Article  PubMed  CAS  Google Scholar 

  197. van de Loo FA, Arntz OJ, van Enckevort FH, et al. (1998) Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2-deficient mice and in anti-interleukin-1-treated wild-type mice with unabated joint inflammation. Arthritis Rheum. 41: 634–646.

    Article  PubMed  Google Scholar 

  198. Rothe H, Kolb H. (1999) Strategies of protection from nitric oxide toxicity in islet inflammation. J. Mol. Med. 77: 40–44.

    Article  PubMed  CAS  Google Scholar 

  199. Grey ST, Arvelo MB, Hasenkamp W, et al. (1999) A20 inhibits cytokine-induced apoptosis and nuclear factor kappa B-dependent gene activation in islets. J. Exp. Med. 190: 1135–1146.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. Whittle BJ. (1997) Nitric oxide-a mediator of inflammation or mucosal defence. Eur. J. Gastroenterol. Hepatol. 9: 1026–1032.

    Article  PubMed  CAS  Google Scholar 

  201. Guslandi M. (1998) Nitric oxide and inflammatory bowel diseases. Eur. J. Clin. Invest. 28: 904–907.

    Article  PubMed  CAS  Google Scholar 

  202. Mourelle M, Vilaseca J, Guarner F, et al. (1996) Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase. Am. J. Physiol. 270: G425–G430.

    PubMed  CAS  Google Scholar 

  203. Kiss J, Lamarque D, Delchier JC, et al. (1997) Time-dependent actions of nitric oxide synthase inhibition on colonic inflammation induced by trinitrobenzene sulphonic acid in rats. Eur. J. Pharmacol. 336: 219–224.

    Article  PubMed  CAS  Google Scholar 

  204. Zingarelli B, Szabo C, Salzman AL. (1999) Blockade of poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis. Gastroenterology 116: 335–345.

    Article  PubMed  CAS  Google Scholar 

  205. Perner A, Rask-Madsen J. (1999) Review article: The potential role of nitric oxide in chronic inflammatory bowel disorders. Aliment. Pharmacol. Ther. 13: 135–144.

    Article  PubMed  CAS  Google Scholar 

  206. Werner J, Rivera J, Fernandez-del CC, et al. (1997) Differing roles of nitric oxide in the pathogenesis of acute edematous versus necrotizing pancreatitis. Surgery 121: 23–30.

    Article  PubMed  CAS  Google Scholar 

  207. McCafferty DM, Mudgett JS, Swain MG, et al. (1997) Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology 112: 1022–1027.

    Article  PubMed  CAS  Google Scholar 

  208. Elliott SN, Wallace JL. (1998) Nitric oxide: A regulator of mucosal defense and injury. J. Gastroenterol. 33: 792–803.

    Article  PubMed  CAS  Google Scholar 

  209. Dimmeler S, Haendeler J, Nehls M, et al. (1997) Suppression of apoptosis by nitric oxide via inhibition of interleukin-1β-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J. Exp. Med. 185: 601–607.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  210. Tzeng E, Kim YM, Pitt BR, et al. (1997) Adenoviral transfer of the inducible nitric oxide synthase gene blocks endothelial cell apoptosis. Surgery 122: 255–263.

    Article  PubMed  CAS  Google Scholar 

  211. Iwashina M, Shichiri M, Marumo F, et al. (1998) Transfection of inducible nitric oxide synthase gene causes apoptosis in vascular smooth muscle cells. Circulation 98: 1212–1218.

    Article  PubMed  CAS  Google Scholar 

  212. Smith JD, McLean SD, Nakayama DK. (1998) Nitric oxide causes apoptosis in pulmonary vascular smooth muscle cells. J. Surg. Res. 79: 121–127.

    Article  PubMed  CAS  Google Scholar 

  213. Chiche JD, Schlutsmeyer SM, Bloch DB, et al. (1998) Adenovirus-mediated gene transfer of cGMP-dependent protein kinase increases the sensitivity of cultured vascular smooth muscle cells to the antiproliferative and pro-apoptotic effects of nitric oxide/cGMP. J. Biol. Chem. 273: 34263–34271.

    Article  PubMed  CAS  Google Scholar 

  214. Best PJ, Hasdai D, Sangiorgi G, et al. (1999) Apoptosis. Basic concepts and implications in coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 19: 14–22.

    Article  PubMed  CAS  Google Scholar 

  215. Zhang HY, Phan SH. (1999) Inhibition of myofibroblast apoptosis by transforming growth factor beta(1). Am. J. Respir. Cell Mol. Biol. 21: 658–665.

    Article  PubMed  CAS  Google Scholar 

  216. Bult H. (1996) Nitric oxide and atherosclerosis: possible implications for therapy. Mol. Med. Today 2: 510–518.

    Article  PubMed  CAS  Google Scholar 

  217. Maxwell AJ, Cooke JP. (1999) The role of nitric oxide in atherosclerosis. Coron. Artery Dis. 10: 277–286.

    Article  PubMed  CAS  Google Scholar 

  218. Ross R. (1999) Atherosclerosis — an inflammatory disease. N. Engl. J. Med. 340: 115–126.

    Article  PubMed  CAS  Google Scholar 

  219. Hunter GC, Henderson AM, Westerband A, et al. (1999) The contribution of inducible nitric oxide and cytomegalovirus to the stability of complex carotid plaque. J. Vasc. Surg. 30: 36–49.

    Article  PubMed  CAS  Google Scholar 

  220. Baker CS, Hall RJ, Evans TJ, et al. (1999) Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler. Thromb. Vasc. Biol. 19: 646–655.

    Article  PubMed  CAS  Google Scholar 

  221. Mallat Z, Heymes C, Ohan J, et al. (1999) Expression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death. Arterioscler. Thromb. Vasc. Biol. 19: 611–616.

    Article  PubMed  CAS  Google Scholar 

  222. Grainger DJ, Kemp PR, Metcalfe JC, et al. (1995) The serum concentration of active transforming growth factor is severely depressed in advanced atherosclerosis. Nat. Med. 1: 74–79.

    Article  PubMed  CAS  Google Scholar 

  223. McCaffrey TA, Consigli S, Du B, et al. (1995) Decreased type II/type I TGF receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-β1. J. Clin. Invest 96: 2667–2675.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  224. Blann AD, Wang JM, Wilson PB, et al. (1996) Serum levels of the TGF receptor are increased in atherosclerosis. Atherosclerosis 120: 221–226.

    Article  PubMed  CAS  Google Scholar 

  225. McCaffrey TA, Du B, Consigli S, et al. (1997) Genomic instability in the type II TGF1 receptor gene in atherosclerotic and restenotic vascular cells [see comments]. J. Clin. Invest 100: 2182–2188.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  226. Scott L, Kerr A, Haydock D, et al. (1997) Subendothelial proteoglycan synthesis and transforming growth factor β distribution correlate with susceptibility to atherosclerosis. J. Vasc. Res. 34: 365–377.

    Article  PubMed  CAS  Google Scholar 

  227. De Sanctis GT, MacLean JA, Hamada K, et al. (1999) Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma. J. Exp. Med. 189: 1621–1630.

    Article  PubMed  PubMed Central  Google Scholar 

  228. Tsuji M, Dimov VB, Yoshida T. (1995) In vivo expression of monokine and inducible nitric oxide synthase in experimentally induced pulmonary granulomatous inflammation. Evidence for sequential production of interleukin-1, inducible nitric oxide synthase, and tumor necrosis factor. Am. J. Pathol. 147: 1001–1015.

    PubMed  PubMed Central  CAS  Google Scholar 

  229. Nozaki Y, Hasegawa Y, Takeuchi A, et al. (1997) Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats. Am. J. Physiol. 272: L651–L658.

    PubMed  CAS  Google Scholar 

  230. Frieri M. (1998) Nitric oxide in allergic rhin it is and asthma. Allergy Asthma Proc. 19: 349–351.

    Article  PubMed  CAS  Google Scholar 

  231. Marshall HE, Stamler JS. (1999) Exhaled nitric oxide (NO), NO synthase activity, and regulation of nuclear factor (NF)-kappa B. Am. J. Respir. Cell Mol. Biol. 21: 296–297.

    Article  PubMed  CAS  Google Scholar 

  232. Long R, Light B, Talbot JA. (1999) Mycobacteriocidal action of exogenous nitric oxide. Antimicrob. Agents Chemother. 43: 403–405.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  233. Buster BL, Weintrob AC, Townsend GC, et al. (1995) Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats. Infect. Immun. 63: 3835–3839.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  234. Leib SL, Kim YS, Black SM, et al. (1998) Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis. J. Infect. Dis. 177: 692–700.

    Article  PubMed  CAS  Google Scholar 

  235. Schaffer MR, Tantry U, Gross SS, et al. (1996) Nitric oxide regulates wound healing. J. Surg. Res. 63: 237–240.

    Article  PubMed  CAS  Google Scholar 

  236. Yamasaki K, Edington HD, McClosky C, et al. (1998) Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J. Clin. Invest. 101: 967–971.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  237. Vodovotz Y. (1997) Control of nitric oxide production by transforming growth factor-beta1: mechanistic insights and potential relevance to human disease. Nitric. Oxide. 1: 3–17.

    Article  PubMed  CAS  Google Scholar 

  238. Ling H, Edelstein C, Gengaro P, et al. (1999) Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice. Am. J. Physiol 277: F383–F390.

    PubMed  CAS  Google Scholar 

  239. Moncada S. (1994) Nitric oxide. J. Hypertens. Suppl. 12: S35–S39.

    PubMed  CAS  Google Scholar 

  240. Cooke JP, Dzau VJ. (1997) Nitric oxide synthase: role in the genesis of vascular disease. Annu. Rev. Med. 48: 489–509.

    Article  PubMed  CAS  Google Scholar 

  241. Sarkar R, Webb RC. (1998) Does nitric oxide regulate smooth muscle cell proliferation? A critical appraisal. J. Vasc. Res. 35: 135–142.

    Article  PubMed  CAS  Google Scholar 

  242. Ruschitzka F, Corti R, Noll G, et al. (1999) A rationale for treatment of endothelial dysfunction in hypertension. J. Hypertens. Suppl 17: S25–S35.

    PubMed  CAS  Google Scholar 

  243. Radomski MW, Zakar T, Salas E. (1996) Nitric oxide in platelets. Methods Enzymol. 269: 88–107.

    Article  PubMed  CAS  Google Scholar 

  244. Cines DB, Pollak ES, Buck CA, et al. (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91: 3527–3561.

    PubMed  CAS  Google Scholar 

  245. Luscher TF, Noll G. (1995) The pathogenesis of cardiovascular disease: role of the endothelium as a target and mediator. Atherosclerosis 118(Suppl): S81–S90.

    Article  PubMed  CAS  Google Scholar 

  246. Liew FY, Xu D, Chan WL. (1999) Immune effector mechanism in parasitic infections. Immunol. Lett. 65: 101–104.

    Article  PubMed  CAS  Google Scholar 

  247. Albina JE, Reichner JS. (1998) Role of nitric oxide in mediation of macrophage cytotoxicity and apoptosis. Cancer Metastasis Rev. 17: 39–53.

    Article  PubMed  CAS  Google Scholar 

  248. Wink DA, Vodovotz Y, Cook JA, et al. (1998) The role of nitric oxide chemistry in cancer treatment. Biochemistry (Mosc.) 63: 802–809.

    CAS  Google Scholar 

  249. Kubes P, Granger DN. (1996) Leukocyte-endothelial cell interactions evoked by mast cells. Cardiovasc. Res. 32: 699–708.

    Article  PubMed  CAS  Google Scholar 

  250. Kojda G, Kottenberg K. (1999) Regulation of basal myocardial function by NO. Cardiovasc. Res. 41: 514–523.

    Article  PubMed  CAS  Google Scholar 

  251. Drexler H, Hornig B. (1999) Endothelial dysfunction in human disease. J. Mol. Cell Cardiol. 31: 51–60.

    Article  PubMed  CAS  Google Scholar 

  252. Schulz R, Nava E, Moncada S. (1992) Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium. Br. J. Pharmacol. 105: 575–580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  253. Roberts AB, Vodovotz Y, Roche NS, et al. (1992) Role of nitric oxide in antagonistic effects of transforming growth factor-beta and interleukin-1 beta on the beating rate of cultured cardiac myocytes. Mol. Endocrinol. 6: 1921–1930.

    PubMed  CAS  Google Scholar 

  254. Zaragoza C, Ocampo C, Saura M, et al. (1998) The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis. Proc. Natl. Acad. Sci. U.S.A. 95: 2469–2474.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  255. Singh S, Evans TW. (1997) Nitric oxide, the biological mediator of the decade: fact or fiction? Eur. Respir. J. 10: 699–707.

    PubMed  CAS  Google Scholar 

  256. Hart CM. (1999) Nitric oxide in adult lung disease. Chest 115: 1407–1417.

    Article  PubMed  CAS  Google Scholar 

  257. Mashimo H, Goyal RK. (1999) Lessons from genetically engineered animal models. IV. Nitric oxide synthase gene knockout mice. Am. J. Physiol. 277: G745–G750.

    PubMed  CAS  Google Scholar 

  258. Sjoholm A. (1998) Aspects of the involvement of interleukin-1 and nitric oxide in the pathogenesis of insulin-dependent diabetes mellitus. Cell Death. Differ. 5: 461–468.

    Article  PubMed  CAS  Google Scholar 

  259. Rabinovitch A, Suarez-Pinzon WL. (1998) Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. Biochem. Pharmacol. 55: 1139–1149.

    Article  PubMed  CAS  Google Scholar 

  260. Muscara MN, Wallace JL. (1999) Nitric oxide. V. Therapeutic potential of nitric oxide donors and inhibitors. Am. J. Physiol 276: G1313–G1316.

    PubMed  CAS  Google Scholar 

  261. Holzer P. (1998) Neural emergency system in the stomach. Gastroenterology 114: 823–839.

    Article  PubMed  CAS  Google Scholar 

  262. Lefer AM, Lefer DJ. (1999) Nitric oxide. II. Nitric oxide protects in intestinal inflammation. Am. J. Physiol 276: G572–G575.

    PubMed  CAS  Google Scholar 

  263. Belmont HM, Levartovsky D, Goel A, et al. (1997) Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum. 40: 1810–1816.

    Article  PubMed  CAS  Google Scholar 

  264. Wigand R, Meyer J, Busse R, et al. (1997) Increased serum NG-hydroxy-l-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of an increased nitric oxide synthase activity. Ann. Rheum. Dis. 56: 330–332.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  265. Gilkeson G, Cannon C, Oates J, et al. (1999) Correlation of serum measures of nitric oxide production with lupus disease activity. J. Rheumatol. 26: 318–324.

    PubMed  CAS  Google Scholar 

  266. Kausalya S, Nath J. (1998) Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury. J. Leukoc. Biol. 64: 185–191.

    Article  PubMed  CAS  Google Scholar 

  267. Harper L, Savage CO. (1999) Mechanisms of endothelial injury in systemic vasculitis. Adv. Nephrol. Necker Hosp. 29: 1–15.

    PubMed  CAS  Google Scholar 

  268. Grabowski PS, Wright PK, Van’t H, et al. (1997) Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis. Br. J. Rheumatol. 36: 651–655.

    Article  PubMed  CAS  Google Scholar 

  269. Borderie D, Hilliquin P, Hernvann A, et al. (1999) Nitric oxide synthase is expressed in the lymphomononuclear cells of synovial fluid in patients with rheumatoid arthritis. J. Rheumatol. 26: 2083–2088.

    PubMed  CAS  Google Scholar 

  270. Amin AR, Attur M, Abramson SB. (1999) Nitric oxide synthase and cyclooxygenases: distribution, regulation, and intervention in arthritis. Curr. Opin. Rheumatol. 11: 202–209.

    Article  PubMed  CAS  Google Scholar 

  271. Kim HA, Song YW. (1999) Apoptotic chondrocyte death in rheumatoid arthritis. Arthritis Rheum. 42: 1528–1537.

    Article  PubMed  CAS  Google Scholar 

  272. McInnes IB, Leung BP, Field M, et al. (1996) Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J. Exp. Med. 184: 1519–1524.

    Article  PubMed  CAS  Google Scholar 

  273. Martel-Pelletier J, Mineau F, Jovanovic D, et al. (1999) Mitogen-activated protein kinase and nuclear factor kappa B together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated proten kinase (MAPKAPK). Arthritis Rheum. 42: 2399–2409.

    Article  PubMed  CAS  Google Scholar 

  274. Salvatierra J, Escames G, Hernandez P, et al. (1999) Cartilage and serum levels of nitric oxide in patients with hip osteoarthritis. J. Rheumatol. 26: 2015–2017.

    PubMed  CAS  Google Scholar 

  275. Hamid Q, Springall DR, Riveros-Moreno V, et al. (1993) Induction of nitric oxide synthase in asthma. Lancet 342: 1510–1513.

    Article  PubMed  CAS  Google Scholar 

  276. Barnes PJ. (1996) Pathophysiology of asthma. Br. J. Clin. Pharmacol. 42: 3–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  277. Wang CH, Hsieh WY, Shih LY, et al. (1999) Increased progenitor cell proliferation in the peripheral blood of patients with bronchial asthma: the role of nitric oxide. J. Allergy Clin. Immunol. 104: 803–810.

    Article  PubMed  CAS  Google Scholar 

  278. Kharitonov SA, Yates D, Barnes PJ. (1995) Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. Eur. Respir. J. 8: 295–297.

    Article  PubMed  CAS  Google Scholar 

  279. Nicholson S, Bonecini-Almeida Md, Silva JR, et al. (1996) Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis. J. Exp. Med. 183: 2293–2302.

    Article  PubMed  CAS  Google Scholar 

  280. Flak TA, Goldman WE. (1996) Autotoxicity of nitric oxide in airway disease. Am. J. Respir. Crit Care Med. 154: S202–S206.

    Article  PubMed  CAS  Google Scholar 

  281. Kwon OJ, Kim JH, Kim HC, et al. (1998) Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation. Respirology. 3: 119–124.

    Article  PubMed  CAS  Google Scholar 

  282. Wang CH, Liu CY, Lin HC, et al. (1998) Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages. Eur. Respir. J. 11: 809–815.

    Article  PubMed  CAS  Google Scholar 

  283. Saleh D, Barnes PJ, Giaid A. (1997) Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 155: 1763–1769.

    Article  PubMed  CAS  Google Scholar 

  284. Rogers DF, Laurent GJ. (1998) New ideas on the pathophysiology and treatment of lung disease. Thorax 53: 200–203.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  285. Paredi P, Kharitonov SA, Loukides S, et al. (1999) Exhaled nitric oxide is increased in active fibrosing alveolitis. Chest 115: 1352–1356.

    Article  PubMed  CAS  Google Scholar 

  286. Tracey WR, Xue C, Klinghofer V, et al. (1994) Immunochemical detection of inducible NO synthase in human lung. Am. J. Physiol. 266: L722–L727.

    Article  PubMed  CAS  Google Scholar 

  287. Barnes PJ. (1995) Nitric oxide and airway disease. Ann. Med. 27: 389–393.

    Article  PubMed  CAS  Google Scholar 

  288. Kharitonov SA, Wells AU, O’Connor BJ, et al. (1995) Elevated levels of exhaled nitric oxide in bronchiectasis. Am. J. Respir. Crit Care Med. 151: 1889–1893.

    Article  PubMed  CAS  Google Scholar 

  289. Leonard N, Bishop AE, Polak JM, et al. (1998) Expression of nitric oxide synthase in inflammatory bowel disease is not affected by corticosteroid treatment. J. Clin. Pathol. 51: 750–753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  290. Singer II, Kawka DW, Scott S, et al. (1996) Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology 111: 871–885.

    Article  PubMed  CAS  Google Scholar 

  291. Gupta SK, Fitzgerald JF, Chong SK, et al. (1998) Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population. Am. J. Gastroenterol. 93: 795–798.

    Article  PubMed  CAS  Google Scholar 

  292. Herulf M, Ljung T, Hellstrom PM, et al. (1998) Increased luminal nitric oxide in inflammatory bowel disease as shown with a novel minimally invasive method. Scand. J. Gastroenterol. 33: 164–169.

    PubMed  CAS  Google Scholar 

  293. Iwashita E, Iwai A, Sawazaki Y, et al. (1998) Activation of microvascular endothelial cells in active ulcerative colitis and detection of inducible nitric oxide synthase. J. Clin. Gastroenterol. 27 (Suppl 1): S74–S79.

    Article  PubMed  Google Scholar 

  294. Ina K, Itoh J, Fukushima K, et al. (1999) Resistance of Crohn’s disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. J. Immunol. 163: 1081–1090.

    PubMed  CAS  Google Scholar 

  295. Izzo AA, Mascolo N, Capasso F. (1998) Nitric oxide as a modulator of intestinal water and electrolyte transport. Dig. Dis. Sci. 43: 1605–1620.

    Article  PubMed  CAS  Google Scholar 

  296. Ford H, Watkins S, Reblock K, et al. (1997) The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J. Pediatr. Surg. 32: 275–282.

    Article  PubMed  CAS  Google Scholar 

  297. Zamora SA, Amin HJ, McMillan DD, et al. (1997) Plasma l-arginine concentrations in premature infants with necrotizing enterocolitis. J. Pediatr. 131: 226–232.

    Article  PubMed  CAS  Google Scholar 

  298. Sigge W, Wedel T, Kuhnel W, et al. (1998) Morphologic alterations of the enteric nervous system and deficiency of non-adrenergic non-cholinergic inhibitory innervation in neonatal necrotizing enterocolitis. Eur. J. Pediatr. Surg. 8: 87–94.

    Article  PubMed  CAS  Google Scholar 

  299. ter Steege J, Buurman W, Arends JW, et al. (1997) Presence of inducible nitric oxide synthase, nitrotyrosine, CD68, and CD14 in the small intestine in celiac disease. Lab. Invest. 77: 29–36.

    PubMed  Google Scholar 

  300. Beckett CG, Dell’Olio D, Ellis HJ, et al. (1998) The detection and localization of inducible nitric oxide synthase production in the small intestine of patients with coeliac disease. Eur. J. Gastroenterol. Hepatol. 10: 641–647.

    PubMed  CAS  Google Scholar 

  301. ter Steege JC, Koster-Kamphuis L, van Straaten EA, et al. (1998) Nitrotyrosine in plasma of celiac disease patients as detected by a new sandwich ELISA. Free Radic. Biol. Med. 25: 953–963.

    Article  PubMed  Google Scholar 

  302. Everts B, Stotzer P, Olsson M, et al. (1999) Increased luminal nitric oxide concentrations in the small intestine of patients with coeliac disease. Eur. J. Clin. Invest 29: 692–696.

    Article  PubMed  CAS  Google Scholar 

  303. Mannick EE, Bravo LE, Zarama G, et al. (1996) Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res. 56: 3238–3243.

    PubMed  CAS  Google Scholar 

  304. Hahm KB, Lee KJ, Choi SY, et al. (1997) Possibility of chemoprevention by the eradication of Helicobacter pylori: Oxidative DNA damage and apoptosis in H. pylori infection. Am. J. Gastroenterol. 92: 1853–1857.

    PubMed  CAS  Google Scholar 

  305. Fu S, Ramanujam KS, Wong A, et al. (1999) Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 116: 1319–1329.

    Article  PubMed  CAS  Google Scholar 

  306. Sakaguchi AA, Miura S, Takeuchi T, et al. (1999) Increased expression of inducible nitric oxide synthase and peroxynitrite in Helicobacter pylori gastric ulcer. Free Radic. Biol. Med. 27: 781–789.

    Article  PubMed  CAS  Google Scholar 

  307. Cattell V, Cook T. (1995) The nitric oxide pathway in glomerulonephritis. Curr. Opin. Nephrol. Hypertens. 4: 359–364.

    Article  PubMed  CAS  Google Scholar 

  308. Kashem A, Endoh M, Yano N, et al. (1996) Expression of inducible-NOS in human glomerulonephritis: The possible source is infiltrating monocytes/macrophages. Kidney Int. 50: 392–399.

    Article  PubMed  CAS  Google Scholar 

  309. Lianos EA. (1998) Activation and potential interactions between the arachidonic acid and l-arginine:nitric oxide pathways in glomerulonephritis. Kidney Int. 53: 540–547.

    Article  PubMed  CAS  Google Scholar 

  310. Cattell V. (1999) Nitric oxide and glomerulonephritis. Semin. Nephrol. 19: 277–287.

    PubMed  CAS  Google Scholar 

  311. Wang JS, Tseng HH, Shih DF, et al. (1997) Expression of inducible nitric oxide synthase and apoptosis in human lupus nephritis. Nephron 77: 404–411.

    Article  PubMed  CAS  Google Scholar 

  312. Furusu A, Miyazaki M, Abe K, et al. (1998) Expression of endothelial and inducible nitric oxide synthase in human glomerulonephritis. Kidney Int. 53: 1760–1768.

    Article  PubMed  CAS  Google Scholar 

  313. Corbett JA, Sweetland MA, Wang JL, et al. (1993) Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans. Proc. Natl. Acad. Sci. U.S.A. 90: 1731–1735.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  314. Vara E, Arias-Diaz J, Garcia C, et al. (1995) Production of TNF alpha, IL-1, IL-6 and nitric oxide by isolated human islets. Transplant. Proc. 27: 3367–3371.

    PubMed  CAS  Google Scholar 

  315. Arnush M, Heitmeier MR, Scarim AL, et al. (1998) IL-1 produced and released endogenously within human islets inhibits beta cell function. J. Clin. Invest 102: 516–526.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  316. Pavlovic D, Chen MC, Bouwens L, et al. (1999) Contribution of ductal cells to cytokine responses by human pancreatic islets. Diabetes 48: 29–33.

    Article  PubMed  CAS  Google Scholar 

  317. Cortesi R, Ascenzi P, Colasanti M, et al. (1998) Cross-enzyme inhibition by gabexate mesylate: formulation and reactivity study. J. Pharm. Sci. 87: 1335–1340.

    Article  PubMed  CAS  Google Scholar 

  318. Sharara AI, Perkins DJ, Misukonis MA, et al. (1997) Interferon (IFN)-alpha activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: Possible relationship of induced NOS2 to the antihepatitis C effects of IFN in vivo. J. Exp. Med. 186: 1495–1502.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  319. Cuzzocrea S, Zingarelli B, Villari D, et al. (1998) Evidence for in vivo peroxynitrite production in human chronic hepatitis. Life Sci. 63: L25–L30.

    Google Scholar 

  320. Lundberg JO, Ehren I, Jansson O, et al. (1996) Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis. Urology 48: 700–702.

    Article  PubMed  CAS  Google Scholar 

  321. Lundberg JO, Lundberg JM, Alving K, et al. (1997) Nitric oxide and inflammation: the answer is blowing in the wind. Nat. Med. 3: 30–31.

    Article  PubMed  CAS  Google Scholar 

  322. Wein AJ. (1997) Nitric oxide and interstitial cystitis. J. Urol. 158: 993.

    PubMed  CAS  Google Scholar 

  323. Ehren I, Hosseini A, Lundberg JO, et al. (1999) Nitric oxide: a useful gas in the detection of lower urinary tract inflammation. J. Urol. 162: 327–329.

    Article  PubMed  CAS  Google Scholar 

  324. Snyder SH. (1996) No NO prevents parkinsonism [comment]. Nat. Med. 2: 965–966.

    Article  PubMed  CAS  Google Scholar 

  325. Hirsch EC, Hunot S, Damier P, et al. (1998) Glial cells and inflammation in Parkinson’s disease: a role in neurodegeneration? Ann. Neurol. 44: S115–S120.

    Article  PubMed  CAS  Google Scholar 

  326. Gerlach M, Blum-Degen D, Lan J, et al. (1999) Nitric oxide in the pathogenesis of Parkinson’s disease. Adv. Neurol. 80: 239–245.

    PubMed  CAS  Google Scholar 

  327. Bagasra O, Michaels FH, Zheng YM, et al. (1995) Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 92: 12041–12045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  328. Parkinson JF, Mitrovic B, Merrill JE. (1997) The role of nitric oxide in multiple sclerosis. J. Mol. Med. 75: 174–186.

    Article  PubMed  CAS  Google Scholar 

  329. Hooper DC, Bagasra O, Marini JC, et al. (1997) Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 94: 2528–2533.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  330. Rouzaut A, Subira ML, de Miguel C, et al. (1999) Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO. Biochim. Biophys. Acta 1451: 319–333.

    Article  PubMed  CAS  Google Scholar 

  331. Adamson DC, Wildemann B, Sasaki M, et al. (1996) Immunologic NO synthase: Elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274: 1917–1921.

    Article  PubMed  CAS  Google Scholar 

  332. Rostasy K, Monti L, Yiannoutsos C, et al. (1999) Human immunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activation: Pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex. Ann. Neurol. 46: 207–216.

    Article  PubMed  CAS  Google Scholar 

  333. Adamson DC, McArthur JC, Dawson TM, et al. (1999) Rate and severity of HIV-associated dementia (HAD): correlations with Gp41 and iNOS. Mol. Med. 5: 98–109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  334. Satoi H, Oka N, Kawasaki T, et al. (1998) Mechanisms of tissue injury in vasculitic neuropathies. Neurology 50: 492–496.

    Article  PubMed  CAS  Google Scholar 

  335. Neufeld AH, Sawada A, Becker B. (1999) Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc. Natl. Acad. Sci. U.S.A. 96: 9944–9948.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  336. Bruch-Gerharz D, Ruzicka T, Kolb-Bachofen V. (1998) Nitric oxide in human skin: current status and future prospects. J. Invest Dermatol. 110: 1–7.

    Article  PubMed  CAS  Google Scholar 

  337. Bruch-Gerharz D, Fehsel K, Suschek C, et al. (1996) A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes. J. Exp. Med. 184: 2007–2012.

    Article  PubMed  CAS  Google Scholar 

  338. Morhenn VB. (1997) Langerhans cells may trigger the psoriatic disease process via production of nitric oxide [see comments]. Immunol. Today 18: 433–436.

    Article  PubMed  CAS  Google Scholar 

  339. McKenzie RC, Weller R. (1998) Langerhans cells, keratinocytes, nitric oxide and psoriasis [letter; comment]. Immunol. Today 19: 427–428.

    Article  PubMed  CAS  Google Scholar 

  340. Kolb-Bachofen V, Bruch-Gerharz D. (1999) Langerhans cells, nitric oxide, keratinocytes and psoriasis [letter]. Immunol. Today 20: 289.

    Article  PubMed  CAS  Google Scholar 

  341. Kuhn A, Fehsel K, Lehmann P, et al. (1998) Aberrant timing in epidermal expression of inducible nitric oxide synthase after UV irradiation in cutaneous lupus erythematosus. J. Invest. Dermatol. 111: 149–153.

    Article  PubMed  CAS  Google Scholar 

  342. Yamamoto T, Katayama I, Nishioka K. (1998) Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis. J. Rheumatol. 25: 314–317.

    PubMed  CAS  Google Scholar 

  343. Yamamoto T, Sawada Y, Katayama I, et al. (1998) Increased production of nitric oxide stimulated by interleukin-1beta in peripheral blood mononuclear cells in patients with systemic sclerosis. Br. J. Rheumatol. 37: 1123–1125.

    Article  PubMed  CAS  Google Scholar 

  344. Cotton SA, Herrick AL, Jayson MI, et al. (1999) Endothelial expression of nitric oxide synthases and nitrotyrosine in systemic sclerosis skin. J. Pathol. 189: 273–278.

    Article  PubMed  CAS  Google Scholar 

  345. Rowe A, Farrell AM, Bunker CB. (1997) Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses. Br. J. Dermatol. 136: 18–23.

    Article  PubMed  CAS  Google Scholar 

  346. Bruch-Gerharz D, Ruzicka T, Kolb-Bachofen V. (1998) Nitric oxide and its implications in skin homeostasis and dise. Arch. Dermatol. Res. 290: 643–651.

    Article  PubMed  CAS  Google Scholar 

  347. Clough GF. (1999) Role of nitric oxide in the regulation of microvascular perfusion in human skin in vivo. J. Physiol (Lond) 516: 549–557.

    Article  CAS  Google Scholar 

  348. Buttery LD, Springall DR, Chester AH, et al. (1996) Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab. Invest. 75: 77–85.

    PubMed  CAS  Google Scholar 

  349. Lafond-Walker A, Chen CL, Augustine S, et al. (1997) Inducible nitric oxide synthase expression in coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis. Am. J. Pathol. 151: 919–925.

    PubMed  PubMed Central  CAS  Google Scholar 

  350. Kinscherf R, Wagner M, Kamencic H, et al. (1999) Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits. Atherosclerosis 144: 33–39.

    Article  PubMed  CAS  Google Scholar 

  351. Takeichi O, Saito I, Hayashi M, et al. (1998) Production of human-inducible nitric oxide synthase in radicular cysts. J. Endod. 24: 157–160.

    Article  PubMed  CAS  Google Scholar 

  352. Takeichi O, Saito I, Okamoto Y, et al. (1998) Cytokine regulation on the synthesis of nitric oxide in vivo by chronically infected human polymorphonuclear leucocytes. Immunology 93: 275–280.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  353. Takeichi O, Hayashi M, Tsurumachi T et al. (1999) Inducible nitric oxide synthase activity by interferon-gamma-producing cells in human radicular cysts. Int. Endod. J. 32: 124–130.

    Article  PubMed  CAS  Google Scholar 

  354. Konttinen YT, Platts LA, Tuominen S, et al. (1997) Role of nitric oxide in Sjogren’s syndrome. Arthritis Rheum. 40: 875–883.

    Article  PubMed  CAS  Google Scholar 

  355. Bacman SR, Berra A, Sterin-Borda L et. al. (1998) Human primary Sjogren’s syndrome autoantibodies as mediators of nitric oxide release coupled to lacrimal gland muscarinic acetylcholine receptors. Curr. Eye Res. 17: 1135–1142.

    Article  PubMed  CAS  Google Scholar 

  356. Ludviksdottir D, Janson C, Hogman M, et al. (1999) Increased nitric oxide in expired air in patients with Sjogren’s syndrome. BHR study group. Bronchial hyperresponsiveness. Eur. Respir. J. 13: 739–743.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruben Zamora.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zamora, R., Vodovotz, Y. & Billiar, T.R. Inducible Nitric Oxide Synthase and Inflammatory Diseases. Mol Med 6, 347–373 (2000). https://doi.org/10.1007/BF03401781

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03401781

Keywords

Navigation