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Cyclic AMP: a selective modulator of NF-κB action

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Abstract

It has been known for several decades that cyclic AMP (cAMP), a prototypical second messenger, transducing the action of a variety of G-protein-coupled receptor ligands, has potent immunosuppressive and anti-inflammatory actions. These actions have been attributed in part to the ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappaB (NF-κB). NF-κB plays a crucial role in switching on the gene expression of a plethora of inflammatory and immune mediators, and as such is one of the master regulators of the immune response and a key target for anti-inflammatory drug design. A number of fundamental molecular mechanisms, contributing to the overall inhibitory actions of cAMP on NF-κB function, are well established. Paradoxically, recent reports indicate that cAMP, via its main effector, the protein kinase A (PKA), also promotes NF-κB activity. Indeed, cAMP actions appear to be highly cell type- and context-dependent. Importantly, several novel players in the cAMP/NF-κB connection, which selectively direct cAMP action, have been recently identified. These findings not only open up exciting new research avenues but also reveal novel opportunities for the design of more selective, NF-κB-targeting, anti-inflammatory drugs.

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References

  1. McKnight GS (1991) Cyclic AMP second messenger systems. Curr Opin Cell Biol 3(2):213–217

    Article  PubMed  CAS  Google Scholar 

  2. Bourne HR, Lichtenstein LM, Melmon KL, Henney CS, Weinstein Y, Shearer GM (1974) Modulation of inflammation and immunity by cyclic AMP. Science 184(132):19–28

    Article  PubMed  CAS  Google Scholar 

  3. Kammer GM (1988) The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response. Immunol Today 9(7–8):222–229

    Article  PubMed  CAS  Google Scholar 

  4. Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M (2008) Cyclic AMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol 39(2):127–132

    Article  PubMed  CAS  Google Scholar 

  5. Tasken K, Ruppelt A (2006) Negative regulation of T-cell receptor activation by the cAMP-PKA-Csk signalling pathway in T-cell lipid rafts. Front Biosci 11:2929–2939

    Article  PubMed  CAS  Google Scholar 

  6. Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733

    Article  PubMed  CAS  Google Scholar 

  7. Greten FR, Karin M (2004) The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer. Cancer Lett 206(2):193–199

    Article  PubMed  CAS  Google Scholar 

  8. Karin M (2005) Inflammation-activated protein kinases as targets for drug development. Proc Am Thorac Soc 2(4):386–390 discussion 394–385

    Article  PubMed  CAS  Google Scholar 

  9. Bockaert J, Pin JP (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J 18(7):1723–1729

    Article  PubMed  CAS  Google Scholar 

  10. Gether U (2000) Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21(1):90–113

    Article  PubMed  CAS  Google Scholar 

  11. Dohlman HG, Thorner J, Caron MG, Lefkowitz RJ (1991) Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem 60:653–688

    Article  PubMed  CAS  Google Scholar 

  12. Gilman A (1987) G Proteins: transducers of receptor-generated signals. Annu Rev Biochem 56:615–649

    Article  PubMed  CAS  Google Scholar 

  13. Premont RT, Gainetdinov RR (2007) Physiological roles of G protein–coupled receptor kinases and arrestins. Annu Rev Physiol 69:511–534

    Article  PubMed  CAS  Google Scholar 

  14. Cooper DM (2003) Regulation and organization of adenylyl cyclases and cAMP. Biochem J 375(Pt 3):517–529

    Article  PubMed  CAS  Google Scholar 

  15. Sunahara RK, Taussig R (2002) Isoforms of mammalian adenylyl cyclase: multiplicities of signaling. Mol Interv 2(3):168–184

    Article  PubMed  CAS  Google Scholar 

  16. Tan CM, Kelvin DJ, Litchfield DW, Ferguson SS, Feldman RD (2001) Tyrosine kinase-mediated ser phosphorylation of adenylyl cyclase. Biochemistry 40(6):1702–1709

    Article  PubMed  CAS  Google Scholar 

  17. Ding Q, Gros R, Gray ID, Taussig R, Ferguson SS, Feldman RD (2004) Raf kinase activation of adenylyl cyclases: isoform-selective regulation. Mol Pharmacol 66(4):921–928

    PubMed  CAS  Google Scholar 

  18. Kawabe J, Iwami G, Ebina T, Ohno S, Katada T, Ueda Y, Homcy CJ, Ishikawa Y (1994) Differential activation of adenylyl cyclase by protein kinase C isoenzymes. J Biol Chem 269(24):16554–16558

    PubMed  CAS  Google Scholar 

  19. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58(3):488–520

    Article  PubMed  CAS  Google Scholar 

  20. Walsh DA, Perkins JP, Krebs EG (1968) An adenosine 3’, 5’-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem 243(13):3763–3765

    PubMed  CAS  Google Scholar 

  21. Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2(8):599–609

    Article  PubMed  CAS  Google Scholar 

  22. Montminy MR, Gonzalez GA, Yamamoto KK (1990) Regulation of cAMP-inducible genes by CREB. Trends Neurosci 13(5):184–188

    Article  PubMed  CAS  Google Scholar 

  23. Bos JL (2003) Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4(9):733–738

    Article  PubMed  CAS  Google Scholar 

  24. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396(6710):474–477

    Article  PubMed  CAS  Google Scholar 

  25. Aronoff DM, Canetti C, Serezani CH, Luo M, Peters-Golden M (2005) Cutting edge: macrophage inhibition by cyclic AMP (cAMP): differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol 174(2):595–599

    PubMed  CAS  Google Scholar 

  26. Bryn T, Mahic M, Enserink JM, Schwede F, Aandahl EM, Tasken K (2006) The cyclic AMP-Epac1-Rap1 pathway is dissociated from regulation of effector functions in monocytes but acquires immunoregulatory function in mature macrophages. J Immunol 176(12):7361–7370

    PubMed  CAS  Google Scholar 

  27. Gerlo S, Verdood P, Kooijman R (2010) Modulation of cytokine production by cyclic adenosine monophosphate analogs in human leukocytes. J Interferon Cytokine Res 30(12):883–891

    Article  PubMed  CAS  Google Scholar 

  28. Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82(3):769–824

    PubMed  CAS  Google Scholar 

  29. Baillie GS, Scott JD, Houslay MD (2005) Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract. FEBS Lett 579(15):3264–3270

    Article  PubMed  CAS  Google Scholar 

  30. Dessauer CW (2009) Adenylyl cyclase–A-kinase anchoring protein complexes: the next dimension in cAMP signaling. Mol Pharmacol 76(5):935–941

    Article  PubMed  CAS  Google Scholar 

  31. Gilmore TD (2006) Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25(51):6680–6684

    Article  PubMed  CAS  Google Scholar 

  32. Gilmore TD, Herscovitch M (2006) Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene 25(51):6887–6899

    Article  PubMed  CAS  Google Scholar 

  33. Hoffmann A, Leung TH, Baltimore D (2003) Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities. EMBO J 22(20):5530–5539

    Article  PubMed  CAS  Google Scholar 

  34. Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293(5534):1495–1499

    Article  PubMed  CAS  Google Scholar 

  35. Perkins ND (2006) Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene 25(51):6717–6730

    Article  PubMed  CAS  Google Scholar 

  36. Vanden Berghe W, Ndlovu MN, Hoya-Arias R, Dijsselbloem N, Gerlo S, Haegeman G (2006) Keeping up NF-kappaB appearances: epigenetic control of immunity or inflammation-triggered epigenetics. Biochem Pharmacol 72(9):1114–1131

    Article  CAS  Google Scholar 

  37. Vanden Berghe W, Vermeulen L, Delerive P, De Bosscher K, Staels B, Haegeman G (2003) A paradigm for gene regulation: inflammation, NF-kappaB and PPAR. Adv Exp Med Biol 544:181–196

    Article  Google Scholar 

  38. Natoli G (2006) Tuning up inflammation: how DNA sequence and chromatin organization control the induction of inflammatory genes by NF-kappaB. FEBS Lett 580(12):2843–2849

    Article  PubMed  CAS  Google Scholar 

  39. Natoli G, Saccani S, Bosisio D, Marazzi I (2005) Interactions of NF-kappaB with chromatin: the art of being at the right place at the right time. Nat Immunol 6(5):439–445

    Article  PubMed  CAS  Google Scholar 

  40. Singh H, Sen R, Baltimore D, Sharp PA (1986) A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature 319(6049):154–158

    Article  PubMed  CAS  Google Scholar 

  41. Bomsztyk K, Toivola B, Emery DW, Rooney JW, Dower SK, Rachie NA, Sibley CH (1990) Role of cAMP in interleukin-1-induced kappa light chain gene expression in murine B cell line. J Biol Chem 265(16):9413–9417

    PubMed  CAS  Google Scholar 

  42. Shirakawa F, Chedid M, Suttles J, Pollok BA, Mizel SB (1989) Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein. Mol Cell Biol 9(3):959–964

    PubMed  CAS  Google Scholar 

  43. Fraser CC (2008) G protein-coupled receptor connectivity to NF-kappaB in inflammation and cancer. Int Rev Immunol 27(5):320–350

    Article  PubMed  CAS  Google Scholar 

  44. Wu X, Mahadev K, Fuchsel L, Ouedraogo R, Xu SQ, Goldstein BJ (2007) Adiponectin suppresses IkappaB kinase activation induced by tumor necrosis factor-alpha or high glucose in endothelial cells: role of cAMP and AMP kinase signaling. Am J Physiol Endocrinol Metab 293(6):E1836–E1844

    Article  PubMed  CAS  Google Scholar 

  45. Kamthong PJ, Wu M (2001) Inhibitor of nuclear factor-kappaB induction by cAMP antagonizes interleukin-1-induced human macrophage-colony-stimulating-factor expression. Biochem J 356(Pt 2):525–530

    Article  PubMed  CAS  Google Scholar 

  46. Watanabe S, Yssel H, Harada Y, Arai K (1994) Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production. Int Immunol 6(4):523–532

    Article  PubMed  CAS  Google Scholar 

  47. Ho HY, Lee HH, Lai MZ (1997) Overexpression of mitogen-activated protein kinase kinase kinase reversed cAMP inhibition of NF-kappaB in T cells. Eur J Immunol 27(1):222–226

    Article  PubMed  CAS  Google Scholar 

  48. Jimenez JL, Punzon C, Navarro J, Munoz-Fernandez MA, Fresno M (2001) Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Ther 299(2):753–759

    PubMed  CAS  Google Scholar 

  49. Navarro J, Punzon C, Jimenez JL, Fernandez-Cruz E, Pizarro A, Fresno M, Munoz-Fernandez MA (1998) Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus type 1 replication and cytokine production in primary T cells: involvement of NF-kappaB and NFAT. J Virol 72(6):4712–4720

    PubMed  CAS  Google Scholar 

  50. Neumann M, Grieshammer T, Chuvpilo S, Kneitz B, Lohoff M, Schimpl A, Franza BR Jr, Serfling E (1995) RelA/p65 is a molecular target for the immunosuppressive action of protein kinase A. EMBO J 14(9):1991–2004

    PubMed  CAS  Google Scholar 

  51. Kikumori T, Kambe F, Nagaya T, Funahashi H, Seo H (2001) Thyrotropin modifies activation of nuclear factor kappaB by tumour necrosis factor alpha in rat thyroid cell line. Biochem J 354(Pt 3):573–579

    Article  PubMed  CAS  Google Scholar 

  52. Chen CC, Chiu KT, Sun YT, Chen WC (1999) Role of the cyclic AMP-protein kinase A pathway in lipopolysaccharide-induced nitric oxide synthase expression in RAW 264.7 macrophages. Involvement of cyclooxygenase-2. J Biol Chem 274(44):31559–31564

    Article  PubMed  CAS  Google Scholar 

  53. Moon EY, Pyo S (2007) Lipopolysaccharide stimulates Epac1-mediated Rap1/NF-kappaB pathway in Raw 264.7 murine macrophages. Immunol Lett 110(2):121–125

    Article  PubMed  CAS  Google Scholar 

  54. Muroi M, Suzuki T (1993) Role of protein kinase A in LPS-induced activation of NF-kappa B proteins of a mouse macrophage-like cell line, J774. Cell Signal 5(3):289–298

    Article  PubMed  CAS  Google Scholar 

  55. Serkkola E, Hurme M (1993) Activation of NF-kappa B by cAMP in human myeloid cells. FEBS Lett 334(3):327–330

    Article  PubMed  CAS  Google Scholar 

  56. Chio CC, Chang YH, Hsu YW, Chi KH, Lin WW (2004) PKA-dependent activation of PKC, p38 MAPK and IKK in macrophage: implication in the induction of inducible nitric oxide synthase and interleukin-6 by dibutyryl cAMP. Cell Signal 16(5):565–575

    Article  PubMed  CAS  Google Scholar 

  57. Suhasini M, Reddy CD, Reddy EP, DiDonato JA, Pilz RB (1997) cAMP-induced NF-kappaB (p50/relB) binding to a c-myb intronic enhancer correlates with c-myb up-regulation and inhibition of erythroleukemia cell differentiation. Oncogene 15(15):1859–1870

    Article  PubMed  CAS  Google Scholar 

  58. Kleinert H, Euchenhofer C, Ihrig-Biedert I, Forstermann U (1996) In murine 3T3 fibroblasts, different second messenger pathways resulting in the induction of NO synthase II (iNOS) converge in the activation of transcription factor NF-kappaB. J Biol Chem 271(11):6039–6044

    Article  PubMed  CAS  Google Scholar 

  59. Yin F, Wang YY, Du JH, Li C, Lu ZZ, Han C, Zhang YY (2006) Noncanonical cAMP pathway and p38 MAPK mediate beta2-adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts. J Mol Cell Cardiol 40(3):384–393

    Article  PubMed  CAS  Google Scholar 

  60. Yoon C, Korade Z, Carter BD (2008) Protein kinase A-induced phosphorylation of the p65 subunit of nuclear factor-kappaB promotes Schwann cell differentiation into a myelinating phenotype. J Neurosci 28(14):3738–3746

    Article  PubMed  CAS  Google Scholar 

  61. Islam KN, Mendelson CR (2002) Potential role of nuclear factor kappaB and reactive oxygen species in cAMP and cytokine regulation of surfactant protein-A gene expression in lung type II cells. Mol Endocrinol 16(6):1428–1440

    Article  PubMed  CAS  Google Scholar 

  62. Wang P, Zhu F, Konstantopoulos K (2010) Prostaglandin E2 induces interleukin-6 expression in human chondrocytes via cAMP/protein kinase A- and phosphatidylinositol 3-kinase-dependent NF-kappaB activation. Am J Physiol Cell Physiol 298(6):C1445–C1456

    Article  PubMed  CAS  Google Scholar 

  63. Dobashi K, Asayama K, Shirahata A (2003) Differential effects of cyclic AMP on induction of nitric oxide synthase in 3T3–L1 cells and brown adipocytes. Free Radic Biol Med 35(1):94–101

    Article  PubMed  CAS  Google Scholar 

  64. Gao N, Hibi Y, Cueno ME, Asamitsu K, Okamoto T (2010) A-kinase interacting protein 1 (AKIP1) acts as a molecular determinant of the role of PKA in NF-{kappa}B signaling. J Biol Chem. 285(36):28097–28104

    Article  PubMed  CAS  Google Scholar 

  65. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M (1997) A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 388(6642):548–554

    Article  PubMed  CAS  Google Scholar 

  66. Farmer P, Pugin J (2000) beta-adrenergic agonists exert their “anti-inflammatory” effects in monocytic cells through the IkappaB/NF-kappaB pathway. Am J Physiol Lung Cell Mol Physiol 279(4):L675–L682

    PubMed  CAS  Google Scholar 

  67. Manna SK, Aggarwal BB (1998) Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol 161(6):2873–2880

    PubMed  CAS  Google Scholar 

  68. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102(11):1296–1301

    PubMed  CAS  Google Scholar 

  69. Chong YH, Shin SA, Lee HJ, Kang JH, Suh YH (2002) Molecular mechanisms underlying cyclic AMP inhibition of macrophage dependent TNF-alpha production and neurotoxicity in response to amyloidogenic C-terminal fragment of Alzheimer’s amyloid precursor protein. J Neuroimmunol 133(1–2):160–174

    Article  PubMed  CAS  Google Scholar 

  70. Delgado M, Ganea D (2001) Inhibition of endotoxin-induced macrophage chemokine production by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide in vitro and in vivo. J Immunol 167(2):966–975

    PubMed  CAS  Google Scholar 

  71. Delgado M, Gonzalez-Rey E, Ganea D (2005) The neuropeptide vasoactive intestinal peptide generates tolerogenic dendritic cells. J Immunol 175(11):7311–7324

    PubMed  CAS  Google Scholar 

  72. Dello Russo C, Boullerne AI, Gavrilyuk V, Feinstein DL (2004) Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1beta production. J Neuroinflammation 1(1):9

    Article  PubMed  CAS  Google Scholar 

  73. Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (2008) Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition. Clinics (Sao Paulo) 63(3):321–328

    Article  Google Scholar 

  74. Li W, Wang T, Ma C, Xiong T, Zhu Y, Wang X (2006) Calcitonin gene-related peptide inhibits interleukin-1beta-induced endogenous monocyte chemoattractant protein-1 secretion in type II alveolar epithelial cells. Am J Physiol Cell Physiol 291(3):C456–C465

    Article  PubMed  CAS  Google Scholar 

  75. Kelschenbach J, Ninkovic J, Wang J, Krishnan A, Charboneau R, Barke RA, Roy S (2008) Morphine withdrawal inhibits IL-12 induction in a macrophage cell line through a mechanism that involves cAMP. J Immunol 180(6):3670–3679

    PubMed  CAS  Google Scholar 

  76. Kim A, Son M, Kim KI, Yang Y, Song EY, Lee HG, Lim JS (2009) Elevation of intracellular cyclic AMP inhibits NF-kappaB-mediated thymosin beta4 expression in melanoma cells. Exp Cell Res 315(19):3325–3335

    Article  PubMed  CAS  Google Scholar 

  77. Kim SY, Seo M, Kim Y, Lee YI, Oh JM, Cho EA, Kang JS, Juhnn YS (2008) Stimulatory heterotrimeric GTP-binding protein inhibits hydrogen peroxide-induced apoptosis by repressing BAK induction in SH-SY5Y human neuroblastoma cells. J Biol Chem 283(3):1350–1361

    Article  PubMed  CAS  Google Scholar 

  78. Chen YJ, Zhang LQ, Wang GP, Zeng H, Lu B, Shen XL, Jiang ZP, Chen FP (2008) Adiponectin inhibits tissue factor expression and enhances tissue factor pathway inhibitor expression in human endothelial cells. Thromb Haemost 100(2):291–300

    PubMed  CAS  Google Scholar 

  79. Garcin G, Le Gallic L, Stoebner PE, Guezennec A, Guesnet J, Lavabre-Bertrand T, Martinez J, Meunier L (2009) Constitutive expression of MC1R in HaCaT keratinocytes inhibits basal and UVB-induced TNF-alpha production. Photochem Photobiol 85(6):1440–1450

    Article  PubMed  CAS  Google Scholar 

  80. Park SY, Lee SW, Shin HK, Chung WT, Lee WS, Rhim BY, Hong KW, Kim CD (2010) Cilostazol enhances apoptosis of synovial cells from rheumatoid arthritis patients with inhibition of cytokine formation via Nrf2-linked heme oxygenase 1 induction. Arthritis Rheum 62(3):732–741

    Article  PubMed  CAS  Google Scholar 

  81. Crisafulli C, Mazzon E, Galuppo M, Paterniti I, Caminiti R, Cuzzocrea S (2010) Olprinone attenuates the development of ischemia/reperfusion injury of the gut. Intensive Care Med 36(7):1235–1247

    Article  PubMed  CAS  Google Scholar 

  82. Hong G, Zhang B, Harbrecht BG (2010) Cyclic AMP inhibits IL-1beta plus IFNgamma-induced NF-kappaB translocation in hepatocytes by a PKA independent mechanism. J Surg Res 159(1):565–571

    Article  PubMed  CAS  Google Scholar 

  83. Spooren A, Kooijman R, Lintermans B, Van Craenenbroeck K, Vermeulen L, Haegeman G, Gerlo S (2010) Cooperation of NFkappaB and CREB to induce synergistic IL-6 expression in astrocytes. Cell Signal 22(5):871–881

    Article  PubMed  CAS  Google Scholar 

  84. Gavrilyuk V, Horvath P, Weinberg G, Feinstein DL (2001) A 27-bp region of the inducible nitric oxide synthase promoter regulates expression in glial cells. J Neurochem 78(1):129–140

    Article  PubMed  CAS  Google Scholar 

  85. Minguet S, Huber M, Rosenkranz L, Schamel WW, Reth M, Brummer T (2005) Adenosine and cAMP are potent inhibitors of the NF-kappa B pathway downstream of immunoreceptors. Eur J Immunol 35(1):31–41

    Article  PubMed  CAS  Google Scholar 

  86. Zhen X, Zhang J, Johnson GP, Friedman E (2001) D(4) dopamine receptor differentially regulates Akt/nuclear factor-kappa b and extracellular signal-regulated kinase pathways in D(4)MN9D cells. Mol Pharmacol 60(4):857–864

    PubMed  CAS  Google Scholar 

  87. Hickey FB, Brereton CF, Mills KH (2008) Adenylate cycalse toxin of Bordetella pertussis inhibits TLR-induced IRF-1 and IRF-8 activation and IL-12 production and enhances IL-10 through MAPK activation in dendritic cells. J Leukoc Biol 84(1):234–243

    Article  PubMed  CAS  Google Scholar 

  88. Ollivier V, Parry GC, Cobb RR, de Prost D, Mackman N (1996) Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells. J Biol Chem 271(34):20828–20835

    Article  PubMed  CAS  Google Scholar 

  89. Takahashi N, Tetsuka T, Uranishi H, Okamoto T (2002) Inhibition of the NF-kappaB transcriptional activity by protein kinase A. Eur J Biochem 269(18):4559–4565

    Article  PubMed  CAS  Google Scholar 

  90. Wall EA, Zavzavadjian JR, Chang MS, Randhawa B, Zhu X, Hsueh RC, Liu J, Driver A, Bao XR, Sternweis PC, Simon MI, Fraser ID (2009) Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95–p105. Sci Signal 2(75):ra28

    Article  PubMed  CAS  Google Scholar 

  91. Delgado M, Ganea D (2001) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit expression of Fas ligand in activated T lymphocytes by regulating c-Myc, NF-kappa B, NF-AT, and early growth factors 2/3. J Immunol 166(2):1028–1040

    PubMed  CAS  Google Scholar 

  92. Hsiung SC, Tin A, Tamir H, Franke TF, Liu KP (2008) Inhibition of 5-HT1A receptor-dependent cell survival by cAMP/protein kinase A: role of protein phosphatase 2A and Bax. J Neurosci Res 86(10):2326–2338

    Article  PubMed  CAS  Google Scholar 

  93. Mustafa SB, Olson MS (1998) Expression of nitric-oxide synthase in rat Kupffer cells is regulated by cAMP. J Biol Chem 273(9):5073–5080

    Article  PubMed  CAS  Google Scholar 

  94. Kloster MM, Naderi EH, Carlsen H, Blomhoff HK, Naderi S (2011) Hyperactivation of NF-kappaB via the MEK signaling is indispensable for the inhibitory effect of cAMP on DNA damage-induced cell death. Mol Cancer 10:45

    Article  PubMed  CAS  Google Scholar 

  95. Davies SP, Reddy H, Caivano M, Cohen P (2000) Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J 351(Pt 1):95–105

    Article  PubMed  CAS  Google Scholar 

  96. Murray AJ (2008) Pharmacological PKA inhibition: all may not be what it seems. Sci Signal 1(22):re4

    Article  PubMed  Google Scholar 

  97. Vermeulen L, De Wilde G, Van Damme P, Vanden Berghe W, Haegeman G (2003) Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J 22(6):1313–1324

    Article  PubMed  CAS  Google Scholar 

  98. Zhong H, SuYang H, Erdjument-Bromage H, Tempst P, Ghosh S (1997) The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell 89(3):413–424

    Article  PubMed  CAS  Google Scholar 

  99. Zhong H, Voll RE, Ghosh S (1998) Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell 1(5):661–671

    Article  PubMed  CAS  Google Scholar 

  100. Dulin NO, Niu J, Browning DD, Ye RD, Voyno-Yasenetskaya T (2001) Cyclic AMP-independent activation of protein kinase A by vasoactive peptides. J Biol Chem 276(24):20827–20830

    Article  PubMed  CAS  Google Scholar 

  101. Gambaryan S, Kobsar A, Rukoyatkina N, Herterich S, Geiger J, Smolenski A, Lohmann SM, Walter U (2010) Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of PKA from an NF-{kappa}B-I{kappa}B complex. J Biol Chem 285(24):18352–18363

    Article  PubMed  CAS  Google Scholar 

  102. Profirovic J, Gorovoy M, Niu J, Pavlovic S, Voyno-Yasenetskaya T (2005) A novel mechanism of G protein-dependent phosphorylation of vasodilator-stimulated phosphoprotein. J Biol Chem 280(38):32866–32876

    Article  PubMed  CAS  Google Scholar 

  103. Sriwai W, Zhou H, Murthy KS (2008) G(q)-dependent signalling by the lysophosphatidic acid receptor LPA(3) in gastric smooth muscle: reciprocal regulation of MYPT1 phosphorylation by Rho kinase and cAMP-independent PKA. Biochem J 411(3):543–551

    Article  PubMed  CAS  Google Scholar 

  104. Vinciguerra M, Hasler U, Mordasini D, Roussel M, Capovilla M, Ogier-Denis E, Vandewalle A, Martin PY, Feraille E (2005) Cytokines and sodium induce protein kinase A-dependent cell-surface Na, K-ATPase recruitment via dissociation of NF-kappaB/IkappaB/protein kinase A catalytic subunit complex in collecting duct principal cells. J Am Soc Nephrol 16(9):2576–2585

    Article  PubMed  CAS  Google Scholar 

  105. Zieger M, Tausch S, Henklein P, Nowak G, Kaufmann R (2001) A novel PAR-1-type thrombin receptor signaling pathway: cyclic AMP-independent activation of PKA in SNB-19 glioblastoma cells. Biochem Biophys Res Commun 282(4):952–957

    Article  PubMed  CAS  Google Scholar 

  106. Spooren A, Kolmus K, Vermeulen L, Van Wesemael K, Haegeman G, Gerlo S (2010) Hunting for ser 276-phosphorylated p65. J Biomed Biotechnol 2010:275892

    Article  PubMed  CAS  Google Scholar 

  107. Guan H, Jiao J, Ricciardi RP (2008) Tumorigenic adenovirus type 12 E1A inhibits phosphorylation of NF-kappaB by PKAc, causing loss of DNA binding and transactivation. J Virol 82(1):40–48

    Article  PubMed  CAS  Google Scholar 

  108. Doucas V, Shi Y, Miyamoto S, West A, Verma I, Evans RM (2000) Cytoplasmic catalytic subunit of protein kinase A mediates cross-repression by NF-kappa B and the glucocorticoid receptor. Proc Natl Acad Sci USA 97(22):11893–11898

    Article  PubMed  CAS  Google Scholar 

  109. Dong J, Jimi E, Zeiss C, Hayden MS, Ghosh S (2010) Constitutively active NF-kappaB triggers systemic TNFalpha-dependent inflammation and localized TNFalpha-independent inflammatory disease. Genes Dev 24(16):1709–1717

    Article  PubMed  CAS  Google Scholar 

  110. Nowak DE, Tian B, Jamaluddin M, Boldogh I, Vergara LA, Choudhary S, Brasier AR (2008) RelA Ser276 phosphorylation is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1 complexes. Mol Cell Biol 28(11):3623–3638

    Article  PubMed  CAS  Google Scholar 

  111. Prasad RC, Wang XL, Law BK, Davis B, Green G, Boone B, Sims L, Law M (2009) Identification of genes, including the gene encoding p27Kip1, regulated by ser 276 phosphorylation of the p65 subunit of NF-kappaB. Cancer Lett 275(1):139–149

    Article  PubMed  CAS  Google Scholar 

  112. Jacque E, Tchenio T, Piton G, Romeo PH, Baud V (2005) RelA repression of RelB activity induces selective gene activation downstream of TNF receptors. Proc Natl Acad Sci USA 102(41):14635–14640

    Article  PubMed  CAS  Google Scholar 

  113. Law M, Corsino P, Parker NT, Law BK (2010) Identification of a small molecule inhibitor of ser 276 phosphorylation of the p65 subunit of NF-kappaB using in silico molecular docking. Cancer Lett 291(2):217–224

    Article  PubMed  CAS  Google Scholar 

  114. Ishinaga H, Jono H, Lim JH, Komatsu K, Xu X, Lee J, Woo CH, Xu H, Feng XH, Chen LF, Yan C, Li JD (2009) Synergistic induction of nuclear factor-kappaB by transforming growth factor-beta and tumour necrosis factor-alpha is mediated by protein kinase A-dependent RelA acetylation. Biochem J 417(2):583–591

    Article  PubMed  CAS  Google Scholar 

  115. Ishinaga H, Jono H, Lim JH, Kweon SM, Xu H, Ha UH, Koga T, Yan C, Feng XH, Chen LF, Li JD (2007) TGF-beta induces p65 acetylation to enhance bacteria-induced NF-kappaB activation. EMBO J 26(4):1150–1162

    Article  PubMed  CAS  Google Scholar 

  116. Yu SH, Chiang WC, Shih HM, Wu KJ (2004) Stimulation of c-Rel transcriptional activity by PKA catalytic subunit beta. J Mol Med 82(9):621–628

    Article  PubMed  CAS  Google Scholar 

  117. Li S, Ni Z, Cong B, Gao W, Xu S, Wang C, Yao Y, Ma C, Ling Y (2007) CCK-8 inhibits LPS-induced IL-1beta production in pulmonary interstitial macrophages by modulating PKA, p38, and NF-kappaB pathway. Shock 27(6):678–686

    Article  PubMed  CAS  Google Scholar 

  118. Qi XF, Kim DH, Yoon YS, Li JH, Song SB, Jin D, Huang XZ, Teng YC, Lee KJ (2009) The adenylyl cyclase-cAMP system suppresses TARC/CCL17 and MDC/CCL22 production through p38 MAPK and NF-kappaB in HaCaT keratinocytes. Mol Immunol 46(10):1925–1934

    Article  PubMed  CAS  Google Scholar 

  119. Rahman A, Anwar KN, Minhajuddin M, Bijli KM, Javaid K, True AL, Malik AB (2004) cAMP targeting of p38 MAP kinase inhibits thrombin-induced NF-kappaB activation and ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol 287(5):L1017–L1024

    Article  PubMed  CAS  Google Scholar 

  120. Zhang J, Bui TN, Xiang J, Lin A (2006) Cyclic AMP inhibits p38 activation via CREB-induced dynein light chain. Mol Cell Biol 26(4):1223–1234

    Article  PubMed  CAS  Google Scholar 

  121. Sousa LP, Carmo AF, Rezende BM, Lopes F, Silva DM, Alessandri AL, Bonjardim CA, Rossi AG, Teixeira MM, Pinho V (2009) Cyclic AMP enhances resolution of allergic pleurisy by promoting inflammatory cell apoptosis via inhibition of PI3 K/Akt and NF-kappaB. Biochem Pharmacol 78(4):396–405

    Article  PubMed  CAS  Google Scholar 

  122. Hou S, Guan H, Ricciardi RP (2003) Phosphorylation of ser 337 of NF-kappaB p50 is critical for DNA binding. J Biol Chem 278(46):45994–45998

    Article  PubMed  CAS  Google Scholar 

  123. Gao N, Asamitsu K, Hibi Y, Ueno T, Okamoto T (2008) AKIP1 enhances NF-kappaB-dependent gene expression by promoting the nuclear retention and phosphorylation of p65. J Biol Chem 283(12):7834–7843

    Article  PubMed  CAS  Google Scholar 

  124. Hoffmann A, Natoli G, Ghosh G (2006) Transcriptional regulation via the NF-kappaB signaling module. Oncogene 25(51):6706–6716

    Article  PubMed  CAS  Google Scholar 

  125. Fraser DA, Arora M, Bohlson SS, Lozano E, Tenner AJ (2007) Generation of inhibitory NFkappaB complexes and phosphorylated cAMP response element-binding protein correlates with the anti-inflammatory activity of complement protein C1q in human monocytes. J Biol Chem 282(10):7360–7367

    Article  PubMed  CAS  Google Scholar 

  126. Dong J, Jimi E, Zhong H, Hayden MS, Ghosh S (2008) Repression of gene expression by unphosphorylated NF-kappaB p65 through epigenetic mechanisms. Genes Dev 22(9):1159–1173

    Article  PubMed  CAS  Google Scholar 

  127. Kim TK, Maniatis T (1997) The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome. Mol Cell 1(1):119–129

    Article  PubMed  CAS  Google Scholar 

  128. McManus KJ, Hendzel MJ (2001) CBP, a transcriptional coactivator and acetyltransferase. Biochem Cell Biol 79(3):253–266

    Article  PubMed  CAS  Google Scholar 

  129. Parry GC, Mackman N (1997) Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription. J Immunol 159(11):5450–5456

    PubMed  CAS  Google Scholar 

  130. Delgado M (2002) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit CBP-NF-kappaB interaction in activated microglia. Biochem Biophys Res Commun 297(5):1181–1185

    Article  PubMed  CAS  Google Scholar 

  131. Delgado M, Ganea D (1999) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit interleukin-12 transcription by regulating nuclear factor kappaB and Ets activation. J Biol Chem 274(45):31930–31940

    Article  PubMed  CAS  Google Scholar 

  132. Delgado M, Ganea D (2001) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit nuclear factor-kappa B-dependent gene activation at multiple levels in the human monocytic cell line THP-1. J Biol Chem 276(1):369–380

    Article  PubMed  CAS  Google Scholar 

  133. Delgado M, Ganea D (2003) Vasoactive intestinal peptide inhibits IL-8 production in human monocytes by downregulating nuclear factor kappaB-dependent transcriptional activity. Biochem Biophys Res Commun 302(2):275–283

    Article  PubMed  CAS  Google Scholar 

  134. Uchiba M, Okajima K, Kaun C, Wojta J, Binder BR (2004) Inhibition of the endothelial cell activation by antithrombin in vitro. Thromb Haemost 92(6):1420–1427

    PubMed  CAS  Google Scholar 

  135. Delgado M, Munoz-Elias EJ, Kan Y, Gozes I, Fridkin M, Brenneman DE, Gomariz RP, Ganea D (1998) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit tumor necrosis factor alpha transcriptional activation by regulating nuclear factor-kB and cAMP response element-binding protein/c-Jun. J Biol Chem 273(47):31427–31436

    Article  PubMed  CAS  Google Scholar 

  136. Harzenetter MD, Novotny AR, Gais P, Molina CA, Altmayr F, Holzmann B (2007) Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER. J Immunol 179(1):607–615

    PubMed  CAS  Google Scholar 

  137. Koga K, Takaesu G, Yoshida R, Nakaya M, Kobayashi T, Kinjyo I, Yoshimura A (2009) Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein. Immunity 30(3):372–383

    Article  PubMed  CAS  Google Scholar 

  138. Safa M, Zand H, Mousavizadeh K, Kazemi A, Bakhshayesh M, Hayat P (2010) Elevation of cyclic AMP causes an imbalance between NF-kappaB and p53 in NALM-6 cells treated by doxorubicin. FEBS Lett 584(15):3492–3498

    Article  PubMed  CAS  Google Scholar 

  139. Chen D, Rothenberg EV (1994) Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles. J Exp Med 179(3):931–942

    Article  PubMed  CAS  Google Scholar 

  140. Vincenti MP, Burrell TA, Taffet SM (1992) Regulation of NF-kappa B activity in murine macrophages: effect of bacterial lipopolysaccharide and phorbol ester. J Cell Physiol 150(1):204–213

    Article  PubMed  CAS  Google Scholar 

  141. Mandrika I, Muceniece R, Wikberg JE (2001) Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. Biochem Pharmacol 61(5):613–621

    Article  PubMed  CAS  Google Scholar 

  142. Gobejishvili L, Barve S, Joshi-Barve S, Uriarte S, Song Z, McClain C (2006) Chronic ethanol-mediated decrease in cAMP primes macrophages to enhanced LPS-inducible NF-kappaB activity and TNF expression: relevance to alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 291(4):G681–G688

    Article  PubMed  CAS  Google Scholar 

  143. Gobejishvili L, Barve S, Joshi-Barve S, McClain C (2008) Enhanced PDE4B expression augments LPS-inducible TNF expression in ethanol-primed monocytes: relevance to alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 295(4):G718–G724

    Article  PubMed  CAS  Google Scholar 

  144. Manna SK, Mukhopadhyay A, Aggarwal BB (2000) Human chorionic gonadotropin suppresses activation of nuclear transcription factor-kappa B and activator protein-1 induced by tumor necrosis factor. J Biol Chem 275(18):13307–13314

    Article  PubMed  CAS  Google Scholar 

  145. Shames BD, McIntyre RC Jr, Bensard DD, Pulido EJ, Selzman CH, Reznikov LL, Harken AH, Meng X (2001) Suppression of tumor necrosis factor alpha production by cAMP in human monocytes: dissociation with mRNA level and independent of interleukin-10. J Surg Res 99(2):187–193

    Article  PubMed  CAS  Google Scholar 

  146. Sarkar A, Sreenivasan Y, Manna SK (2003) alpha-Melanocyte-stimulating hormone induces cell death in mast cells: involvement of NF-kappaB. FEBS Lett 549(1–3):87–93

    Article  PubMed  CAS  Google Scholar 

  147. Zhou W, Hashimoto K, Goleniewska K, O’Neal JF, Ji S, Blackwell TS, Fitzgerald GA, Egan KM, Geraci MW, Peebles RS Jr (2007) Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. J Immunol 178(2):702–710

    PubMed  CAS  Google Scholar 

  148. Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, Carmo AF, Russo RC, Garcia CC, Bonjardim CA, Alessandri AL, Rossi AG, Pinho V, Teixeira MM (2010) PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3 K/Akt-dependent and NF-{kappa}B-independent manner. J Leukoc Biol 87:895–904

    Article  PubMed  CAS  Google Scholar 

  149. Cavicchi M, Whittle BJ (1999) Potentiation of cytokine induced iNOS expression in the human intestinal epithelial cell line, DLD-1, by cyclic AMP. Gut 45(3):367–374

    Article  PubMed  CAS  Google Scholar 

  150. Hershko DD, Robb BW, Luo G, Hasselgren PO (2002) Multiple transcription factors regulating the IL-6 gene are activated by cAMP in cultured Caco-2 cells. Am J Physiol Regul Integr Comp Physiol 283(5):R1140–R1148

    PubMed  Google Scholar 

  151. Haddad JJ, Land SC, Tarnow-Mordi WO, Zembala M, Kowalczyk D, Lauterbach R (2002) Immunopharmacological potential of selective phosphodiesterase inhibition. II. Evidence for the involvement of an inhibitory-kappaB/nuclear factor-kappaB-sensitive pathway in alveolar epithelial cells. J Pharmacol Exp Ther 300(2):567–576

    Article  PubMed  CAS  Google Scholar 

  152. Rao Ch V, Li X, Manna SK, Lei ZM, Aggarwal BB (2004) Human chorionic gonadotropin decreases proliferation and invasion of breast cancer MCF-7 cells by inhibiting NF-kappaB and AP-1 activation. J Biol Chem 279(24):25503–25510

    Article  PubMed  CAS  Google Scholar 

  153. Holden NS, Rider CF, Bell MJ, Velayudhan J, King EM, Kaur M, Salmon M, Giembycz MA, Newton R (2010) Enhancement of inflammatory mediator release by beta(2)-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action. Br J Pharmacol 160(2):410–420

    Article  PubMed  CAS  Google Scholar 

  154. Ghersa P, Hooft van Huijsduijnen R, Whelan J, Cambet Y, Pescini R, DeLamarter JF (1994) Inhibition of E-selectin gene transcription through a cAMP-dependent protein kinase pathway. J Biol Chem 269(46):29129–29137

    PubMed  CAS  Google Scholar 

  155. Otsuki M, Saito H, Xu X, Sumitani S, Kouhara H, Kurabayashi M, Kasayama S (2001) Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-kappaB binding to its recognition sequence. Atherosclerosis 158(1):121–128

    Article  PubMed  CAS  Google Scholar 

  156. Newman WH, Zhang LM, Lee DH, Dalton ML, Warejcka DJ, Castresana MR, Leeper-Woodford SK (1998) Release of tumor necrosis factor-alpha from coronary smooth muscle: activation of NF-kappaB and inhibition by elevated cyclic AMP. J Surg Res 80(2):129–135

    Article  PubMed  CAS  Google Scholar 

  157. Ammit AJ, Hoffman RK, Amrani Y, Lazaar AL, Hay DW, Torphy TJ, Penn RB, Panettieri RA Jr (2000) Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth-muscle cells. Modulation by cyclic adenosine monophosphate. Am J Respir Cell Mol Biol 23(6):794–802

    PubMed  CAS  Google Scholar 

  158. Kim NY, Pae HO, Kim YC, Choi CK, Rim JS, Lee HS, Kim YM, Chung HT (2000) Pentoxifylline potentiates nitric oxide production in interleukin-1beta-stimulated vascular smooth muscle cells through cyclic AMP-dependent protein kinase A pathway. Gen Pharmacol 35(4):205–211

    Article  PubMed  CAS  Google Scholar 

  159. Aizawa T, Wei H, Miano JM, Abe J, Berk BC, Yan C (2003) Role of phosphodiesterase 3 in NO/cGMP-mediated antiinflammatory effects in vascular smooth muscle cells. Circ Res 93(5):406–413

    Article  PubMed  CAS  Google Scholar 

  160. Kaur M, Holden NS, Wilson SM, Sukkar MB, Chung KF, Barnes PJ, Newton R, Giembycz MA (2008) Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A. Am J Physiol Lung Cell Mol Physiol 295(3):L505–L514

    Article  PubMed  CAS  Google Scholar 

  161. Aoki C, Hattori Y, Tomizawa A, Jojima T, Kasai K (2010) Anti-inflammatory role of cilostazol in vascular smooth muscle cells in vitro and in vivo. J Atheroscler Thromb 17(5):503–509

    Article  PubMed  CAS  Google Scholar 

  162. Woo MS, Jang PG, Park JS, Kim WK, Joh TH, Kim HS (2003) Selective modulation of lipopolysaccharide-stimulated cytokine expression and mitogen-activated protein kinase pathways by dibutyryl-cAMP in BV2 microglial cells. Brain Res Mol Brain Res 113(1–2):86–96

    Article  PubMed  CAS  Google Scholar 

  163. Satriano J, Schlondorff D (1994) Activation and attenuation of transcription factor NF-kB in mouse glomerular mesangial cells in response to tumor necrosis factor-alpha, immunoglobulin G, and adenosine 3′:5′-cyclic monophosphate. Evidence for involvement of reactive oxygen species. J Clin Invest 94(4):1629–1636

    Article  PubMed  CAS  Google Scholar 

  164. Grassl C, Luckow B, Schlondorff D, Dendorfer U (1999) Transcriptional regulation of the interleukin-6 gene in mesangial cells. J Am Soc Nephrol 10(7):1466–1477

    PubMed  CAS  Google Scholar 

  165. Combes P, Dickenson JM (2001) Inhibition of NF-kappaB-mediated gene transcription by the human A2B adenosine receptor in Chinese hamster ovary cells. J Pharm Pharmacol 53(8):1153–1156

    Article  PubMed  CAS  Google Scholar 

  166. Kamthong PJ, Wu FM, Wu MC (2000) cAMP attenuates interleukin-1-stimulated macrophage colony-stimulating factor (M-CSF) expression. Biochem J 350(Pt 1):115–122

    Article  PubMed  CAS  Google Scholar 

  167. Harbrecht BG, Taylor BS, Xu Z, Ramalakshmi S, Ganster RW, Geller DA (2001) cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding activity in cultured rat hepatocytes. J Surg Res 99(2):258–264

    Article  PubMed  CAS  Google Scholar 

  168. Batmunkh C, Krajewski J, Jelkmann W, Hellwig-Burgel T (2006) Erythropoietin production: Molecular mechanisms of the antagonistic actions of cyclic adenosine monophosphate and interleukin-1. FEBS Lett 580(13):3153–3160

    Article  PubMed  CAS  Google Scholar 

  169. Yamaguchi K, Kawahara T, Kumakura S, Hua J, Kugimiya T, Nagaoka I, Inada E (2010) Effect of olprinone, a phosphodiesterase III inhibitor, on hepatic ischemiareperfusion injury in rats. Shock 33(4):436–441

    Article  PubMed  CAS  Google Scholar 

  170. Dendorfer U, Oettgen P, Libermann TA (1995) Interleukin-6 gene expression by prostaglandins and cyclic AMP mediated by multiple regulatory elements. Am J Ther 2(9):660–665

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Fund for Scientific Research Flanders (FWO). K. Kolmus and A. Spooren are FWO predoctoral fellows and I. Beck is an FWO postdoctoral fellow. S. Gerlo is an FWO postdoctoral fellow and supported by the Ghent University GROUP-ID consortium.

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  1. VIB Department of Medical Protein Research, Ghent University (UGent), Albert Baertsoenkaai 3, 9000, Ghent, Belgium

    Sarah Gerlo & Krzysztof Kolmus

  2. Department of Pharmacology, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium

    Ron Kooijman

  3. Laboratory of Eukaryotic Signal Transduction and Gene Expression (LEGEST), Ghent University (UGent), K.L. Ledeganckstraat 35, 9000, Ghent, Belgium

    Sarah Gerlo, Ilse M. Beck, Krzysztof Kolmus, Anneleen Spooren & Guy Haegeman

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Correspondence to Sarah Gerlo.

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Gerlo, S., Kooijman, R., Beck, I.M. et al. Cyclic AMP: a selective modulator of NF-κB action. Cell. Mol. Life Sci. 68, 3823–3841 (2011). https://doi.org/10.1007/s00018-011-0757-8

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