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Inhibition of Human and Rat Glial Cell Function by Anti-Inflammatory Cytokines, Antioxidants, and Elevators of cAMP

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Cell Biology and Pathology of Myelin

Part of the book series: Altschul Symposia Series ((ALSS,volume 4))

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Abstract

There is accumulating evidence for the involvement of tumor necrosis factor alpha (TNFα) and nitric oxide (NO), produced as a consequence of activation of inducible nitric oxide synthase (iNOS), in Multiple Sclerosis (MS). The same evidence has been found in the animal model of MS, experimental allergic encephalomyelitis (EAE). EAE brains and spinal cords have elevated levels of iNOS and NO correlating with the severity and stage of the disease. Aminoguanidine, an inhibitor of iNOS, ameliorates EAE. Inducible NOS mRNA and protein have been detected in MS brain and footprints of NO seen in serum and spinal fluid of MS patients (reviewed in Parkinson et al., in press). TNFa is also elevated in MS patients’ central nervous system (CNS) as well as in EAE, where the interference with the TNFα receptor or TNFa itself antagonizes the disease in the mouse model. The functional removal of macrophages or the pretreatment of EAE animals with Interleukin 4 (IL4), Interleukin 10 (ILIO), or Interleukin 13 (IL13), which downregulate class II major histocompatability molecules, ILl and TNFα, inhibit clinical and histological EAE (de Waal Melefyt et al., 1991; Khoury et al., 1992; reviewed in Merrill and Benveniste, in press).

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References

  • Althaus JS Oien TT Fici GJ Scherch HM Sethy VH and vonVoigtlander PF (1994): Structure activity relationships of peroxynitrite scavengers: an approach to nitric oxide neurotoxicitry. Res. Comm. Chem. Pathol. Pharmacol. 83: 243–252.

    CAS  Google Scholar 

  • Andersen HU Larsen PM Fey SJ Karlsen AE Mandrup-Poulsen T and Nerup J (1995): Two dimensional gel electrophoresis of rat islet proteins. Interleukinl0-induced changes in protein expression are reduced by L-arginine depletion and nicotinamide. Diabetes 44: 400–407.

    Article  Google Scholar 

  • Betz Corradin S Fase1 N Buchmüller-Rouiller Y Ransijn A Smith J and Mauël J (1993): Induction of macrophage nitric oxide production by interferon-y and tumor necrosis factor -a is enhanced by interleukin-10. Eur. J. Immunol. 23: 2045–2048.

    Article  Google Scholar 

  • Biswas DK Dezube BJ Ahlers CM and Pardee AB (1993): Pentoxifylline inhibits HIV-1 LTR-driven gene expression by blocking NF-KB action. J. AIDS 6: 778–786

    CAS  Google Scholar 

  • Bogdan C Stenger S Röllinghoff M and Solbach W (1991a): Cytokine interactions in experimental cutaneous leishmaniasis. Interleukin 4 synergizes with interferon-y to activate murine macrophages for killing of Leishmania majoramastigotes. Eur. J. Immunol. 21: 327–333.

    Article  CAS  Google Scholar 

  • Bogdan C Vodovotz T and Nathan C (1991b): Macrophage deactivation by interleukin 10. J. Exp. Med. 174: 1549–1555.

    Article  CAS  Google Scholar 

  • Bogdan C Vodovotz T Paik J Xie Q and Nathan C (1994): Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages. J. Leukoc. Biol. 55: 227–233.

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Cash E Minty A Ferrara P Caput D Fradelizi D and Rott I (1994): Macrophage-inactivating 1L-13 suppresses experimental autoimmune encephalomyelitis in rats. J. lmmunol. 153: 4258–4267.

    CAS  Google Scholar 

  • Cenci E Romani L Mencacci A Spaccapelo R Schiaffela E Puccetti P and Bistoni F (1993): Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing of Candida aihican.s. Eur. J. Immunol. 23: 1034–1038.

    Article  PubMed  CAS  Google Scholar 

  • Cetkovic-Cvrlje M Sandler S and Eizirik DL (1993): Nicotinamide and dexamethasone inhibit interleukin-1 induced nitric oxide production by RINm5F cells without decreasing messenger ribonucleic acid expression for nitric oxide synthase. Endocrinol. 133: 1739–1743.

    Article  CAS  Google Scholar 

  • Chao CC Hu S Close K Choi CS Molitor TW Novick WJ and Peterson PK (1992): Cytokine release from micro-glia: Differential inhibition by pentoxifylline and dexamethasone. J. Infect. Dis. 166: 847–853.

    Article  PubMed  CAS  Google Scholar 

  • Chao CC Molitor TW and Hu S (1993): Neuroprotective role of IL-4 against activated microglia. J. Immunol. 151: 1473–1481.

    PubMed  CAS  Google Scholar 

  • Cunha FQ Moncada S and Liew FY (1992): Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-y in murine macrophages. Biochem. Biophys. Res. Comm. 182: 1155–1159.

    CAS  Google Scholar 

  • Deguchi M Inaba K and Muramatsu S (1995): counteracting effect of interferon-a and-ß on the interferon-y-induced production of nitric oxide which is suppressive for antibody response. Immunol. Letts. 45: 157–162.

    Article  CAS  Google Scholar 

  • de Waal Malefyt R Abrams J Bennett B Figdor CG and de Vries JE (1991): Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J. Exp. Med. 174; 1209–1220.

    Article  Google Scholar 

  • Doyle AG Herbein G Montaner LJ Minty AJ Caput D Ferrara P and Gordon s (1994): interleukin-13 alters the activation state of murine macrophages in vitro: comparison with interleukin-4 and interferon-y. Eur. J. Immunol. 24:1441–1445.

    Article  PubMed  CAS  Google Scholar 

  • Dröge W Schulze-Osthoff K Mihm S Gaiter D Schenk H Eck H-P Roth S and Gmünder H (1994): Functions of glutathione and glutathione disulfide in immunology and immunopathology. FASEB J. 8: 1131–1138.

    PubMed  Google Scholar 

  • Fast DJ Lynch RC Leu RW (1993): Interferon-y, but not interferon-aß, synergizes with tumor necrosis factor-a and lipid A in the induction of nitric oxide production by murine L929 cells. J. Interferon Res. 13: 271–277.

    Article  PubMed  CAS  Google Scholar 

  • Feinstein, DL Galea E and Reis DJ (1993): Norepinephrine suppresses inducible nitric oxide synthase activity in rat astroglial cultures. J. Neurochem. 60: 1945–1948.

    Article  PubMed  CAS  Google Scholar 

  • Fiorentino DF Zlotnik A Mosmann TR Howard M and O’Garra A (1991): IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 147: 3815–3822.

    PubMed  CAS  Google Scholar 

  • Fujihara M Ito N Pace JL Watanabe Y Russell SW and Suzuki T (1994): Role of endogenous interferon-ß in lipopolysaccharide-triggered activation of the inducible nitric oxide synthase gene in a mouse macrophage cell line, J774. J. Biol. Chem. 269: 12773–12778.

    PubMed  CAS  Google Scholar 

  • Gaiter D Mihm S and Dröge W (1994): Distinct effects of glutathione disulphide on the nuclear transcription factors kB and the activator protein-1. Eur. J. Biochem. 864: 639–648.

    Google Scholar 

  • Gazzinelli, R. T., Oswald, I. P., James, S. L., and Sher, A. (1992). IL10 inhibits parasite killing and nitrogen oxide production by IFN-y-activated macrophages. J. Immunol., 148. 1792–1796.

    PubMed  CAS  Google Scholar 

  • Genain CP Roberts T Davis RL Nguyen M-H Uccelli A Faulds D Li Y Hedgpeth J and Hauser SL (1995): Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor. Proc. Natl. Acad. Sci. 92: 3601–3605.

    Article  PubMed  CAS  Google Scholar 

  • Han J Thompson P and Beutler B (1990): Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J. Exp. Med. 172: 391–394.

    Article  PubMed  CAS  Google Scholar 

  • Hauschildt S Scheipers P and Bessler WG (1991): Inhibitors of poly (ADP-ribose) polymerase suppress lipopolysacchardie-induced nitrite formation in macrophages. Biochem. Biophys. Res. Comm. 179: 865–871.

    CAS  Google Scholar 

  • Hayashi T ueno Y and Okamoto T (1993): Oxidoreductive regulation of nuclear factor KB. Involvement of a cellular reducing catalyst thioredoxin. J. Biol. Chem 268: 11380–11388.

    PubMed  CAS  Google Scholar 

  • Ignarro LJ Lipton H Edwards JC Baricos WH Hyman AL Kadowitz RI and Gruetter GA (1981): Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside, and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates. J. Pharmacol. Exp. Therapeutics 218: 739–743.

    CAS  Google Scholar 

  • Kambashi T Jacob CO Zhou D Mazurek N Fong M and Strassmann G (1995): cyclic nucleotide phosphodiesterase type IV participates in the regulation of IL-10 and in the subsequent inhibition of TNF-a and IL-6 release by endotoxin-stimulated macrophages. J. Immunol. 155: 4909–4916.

    Google Scholar 

  • Kennedy MK Torrance DS Picha KS and Mohler KM (1992): Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J. Immunol. 149: 2496–2505.

    PubMed  CAS  Google Scholar 

  • Khoury Si Hancock WW and Weiner HL (1992): Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor ß, interleukin 4, and prostaglandin E expression in the brain. J. Exp. Med. 176: 1355–1364.

    CAS  Google Scholar 

  • Koka P He K Zack JA Kitchen S Peacock W Fried I Tran T Yashar SS and Merrill JE (1995): Human immunodeficiency virus I envelope proteins induce interleukin 1, tumor necrosis factor a, and nitric oxide in glial cultures derived from fetal. neonatal, and adult human brain. J. Exp. Med. 182: 941–952.

    Article  PubMed  CAS  Google Scholar 

  • Kozaki H Egawa H Bermudes L Feduska NJ So S and Esquivel CO (1993): Pentoxifylline inhibits production of superoxide anion and tumor necrosis factot by kupffer cells in rat liver preservation. Transplant. Proc. 25: 3025–3026.

    CAS  Google Scholar 

  • Kreil TR and Eibl MM (1995): Viral infection of macrophages profoundly alters requirements for induction of nitric oxide snthesis. Virol. 212: 174–178.

    Article  CAS  Google Scholar 

  • Kröncke KD Funda J Berschick B Kolb H and Kolb-Bachofen V (1991): Macrophage cytotoxicity towards isolated rat islet cells: neither lysis nor its protection by nicotinamide’ are beta cell specific. Diabetol. 34: 232–238.

    Article  Google Scholar 

  • Liew FY Li Y Severn A Millot S Schmidt J Salter M and Moncada S (1991): A possible novel pathway of regulation by murine T helper type-2 (T52) cells of a Th I cell activity via the modulation of the induction of nitric oxide synthase on macrophages. Eur. J. Immunol. 21: 2489–2494.

    Article  PubMed  CAS  Google Scholar 

  • MacMicking JD Nathan C Horn G Chartrain N Fletcher DS Trumbauer M Stevens K Xie Q-W Sokol K Hutchinson N Chen H and Mudgett JS (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 

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

    CAS  Google Scholar 

  • Mayer M and Noble M (1994): N-acetyl-L-cysteine is a pluripotent protector against cell death and enhancer of trophic factor-mediated cell survival in vitro. Proc. Natl. Acad. Sci. 91: 7496–7500.

    Article  PubMed  CAS  Google Scholar 

  • Merrill JE and Benveniste EN (1996): Cytokines in inflammatory brain lesions: helpful and harmful. TINS 19: 331–338.

    PubMed  CAS  Google Scholar 

  • Merrill, JE Ignarro LJ Sherman MP Melinek J and Lane TE (1993): Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J. Immunol.,151,; 2132–2141.

    PubMed  CAS  Google Scholar 

  • Nabioullin R Sone S Mizuno K Yano S Nishioka Y Haku T and Ogura T (1994): Interleukin-10 is a potent inhibi-tor of tumor cytotoxicity by human monocytes and alveolar macrophages. J. Leukoc. Biol. 55: 437–442.

    Google Scholar 

  • Oswald IP Gazzinelli RT Sher A and James SL (1992a): IL10 synergizes with IL-4 and transforming growth fac-tor-13 to inhibit macrophage cytotoxic activity. J. Immunol. 148: 3578–3582.

    CAS  Google Scholar 

  • Oswald IP Wynn TA Sher A and James SL (1992b): Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor a required as a costimulatory factor for interferon y-induced activation. Proc. Natl. Acad. Sci. USA 89: 8676–8680.

    Article  CAS  Google Scholar 

  • Oswald IP Wynn TA Sher A and James SL (1992b): Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor a required as a costimulatory factor for interferon y-induced activation. Proc. Natl. Acad. Sci. USA 89: 8676–8680.

    Article  CAS  Google Scholar 

  • Pellat-Deceunynck C Wietzerbin J and Drapier J-C (1994): Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages. Biochem. J. 297: 53–58.

    PubMed  CAS  Google Scholar 

  • Rott O Cash E and Fleischer B (1993): Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1- but not type 2-associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats. Eur. J. Immunol. 23: 1745–1751.

    Article  PubMed  CAS  Google Scholar 

  • Rott O Fleischer B and Cash E (1994): Interleukin-10 prevents experimental allergic encephalomyelitis in rats. Eur. J. Immunol. 24: 1434–1440.

    Article  PubMed  CAS  Google Scholar 

  • Saura M Martinez-Dalmau R Minty A Perez-Sala D and Lamas S (1996): Interleukin-l3 inhibits inducible nitric oxide synthase expression in humnan mesangial cells. Biochem. J. 313: 641–6646.

    PubMed  CAS  Google Scholar 

  • Schreck R Meier B Männel DN Dröge W and Baeuerle PA (1992): Dithiocarbamates as potent inhibitors of nuclear factor KB activation in intact cells. J. Exp. Med. 175: 1181–1194.

    Article  PubMed  CAS  Google Scholar 

  • Sommer N Löschmann P-A Northoff GH Weller M Steinbrecher A Steinbach JP Lichtenfels R Meyerrnann R Riethmüller A Fontana A Dichgans J and Martin R (1995): The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. Nature Med. I: 244–248.

    Article  Google Scholar 

  • Strassmann G Patil-Koota V Finkelman F Fong M and Kambayashi (1994): Evidence for the involvement of interleukin 10 in the differential deactivation of murine peritoneal macrophages by prostaglandin E, J. exp. Med. 180: 2365–2370.

    Article  PubMed  CAS  Google Scholar 

  • Stricter RM Remick DG Ward PA Spengler RN Lynch Ill JP Larrick J and Kunkel SL (1988): Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem. Biophys. Res. Comm. 155: 1230–1236.

    Google Scholar 

  • Takahashi GW Montgomery RB Stahl WL Crittenden CA Valentine MA Thoming DR Andrews Ill DF and Lilly MB (1994): Pentoxifylline inhibits tumor necrosis factor-a-mediated cytotoxicity and cytostasis in L929 murine fibrosarcoma cells. Int. J. Immunopharmac. 16: 723–736.

    Article  CAS  Google Scholar 

  • Zajicek JP Wing M Scolding NJ and Compston DAS (1992): Interactions between oligodendrocytes and micro-glia. Brain 115: 1611–1631.

    PubMed  Google Scholar 

  • Zhang X Alley EW Russell SW and Morrison DC (1994): Necessity and sufficiency of beta interferon for nitric oxide production in mouse peritoneal macrophages. Infect. Immunity 62: 33–40.

    CAS  Google Scholar 

  • Zhou A Chen Z Rummage JA Jiang H Kolosov M Kolosova I Stewart CA and Leu RW (1995): Exogenous interferon-y induces endogenous synthesis of interferon-a and-ß by murine macrophages for induction of nitric oxide synthase. J. Interferon Res. 15: 897–904.

    Article  CAS  Google Scholar 

  • Zingarelli B O’Connor M Wong H Salzman AL and Szabó C (1996): Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated wwith bacterial lipopolysaccharide. J. immunol. 156: 350–358.

    PubMed  CAS  Google Scholar 

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St. Pierre, B., Wong, J.L., Merrill, J.E. (1997). Inhibition of Human and Rat Glial Cell Function by Anti-Inflammatory Cytokines, Antioxidants, and Elevators of cAMP. In: Juurlink, B.H.J., Devon, R.M., Doucette, J.R., Nazarali, A.J., Schreyer, D.J., Verge, V.M.K. (eds) Cell Biology and Pathology of Myelin. Altschul Symposia Series, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5949-8_26

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  • DOI: https://doi.org/10.1007/978-1-4615-5949-8_26

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