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Molecular and cellular aspects of cytokine regulation by glucocorticoids

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Glucocorticoids

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

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Abstract

Glucocorticoids (GC) are potent immunosuppressive agents that have been successfully used in the management of several disorders associated with heightened immunity including transplant rejection, autoimmune diseases and inflammatory disorders [1]. Lymphocytes and macrophages, as primary effectors of cellular and humoral immune responses, are the main targets of their immunoregulatory action [2–10].

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References

  1. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE (1993) Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 119: 1198–1208

    PubMed  CAS  Google Scholar 

  2. Boumpas DT, Paliogianni F, Anastassiou ED, Balow (1991) Glucocorticosteroid action on the immune system: molecular and cellular aspects. Clin Exp Rheumatol 9: 413–423

    PubMed  CAS  Google Scholar 

  3. Paliogianni F, Ahuja SS, Yamada H, Balow JP, Boumpas DT (1992) Glucocorticoids inhibit T cell proliferation by downregulating proliferative signals mediated through both T cell antigen and interleukin-2 receptors. Arthritis Rheum 35: S 127 (Abstract)

    Article  Google Scholar 

  4. Vacca A, Screpanti I, Maroder M, Felli MP, Farina AR, Gismondi A, Santoni A, Fracti A, Gulino A (1990) Transcriptional regulation of the interleukin-2 gene by glucocorticoid hormones. J Biol Chem 265: 8075–8080

    PubMed  CAS  Google Scholar 

  5. Adcock IM, Brown CR, Gelder CM, Shirasaki H, Peters MJ, Barnes PJ (1995) Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cell. Amer J Physiol268 (2pt 1): C331–C338

    PubMed  CAS  Google Scholar 

  6. Paliogianni F, Ahuja SS, Balow JP, Boumpas DT (1993) Novel mechanism for inhibition of human T cells by glucocorticoids (GC): GC modulate signal transduction through IL-2 receptor. J Immunol 151: 4081–4089

    PubMed  CAS  Google Scholar 

  7. Bowen DL, Fauci AS (1988) Adrenal corticosteroids. In: JI Gallin, IM Goldstein, R Snyderman (eds): Inflammation: basic and clinical correlates. Haven Press, New York, 935–946

    Google Scholar 

  8. Amano Y, Lee SW, Allison AC (1993) Inhibition by glucocorticoids of the formation of inter-leukin-la, interkeukin-lp, and interleukin-6: mediation by decrease mRNA stability. Mol Pharmacol A3: 176–182

    Google Scholar 

  9. Lee SW, Tsuo AP, Chan H, Thomas J, Petrick Eugui EM, Allison AC (1988) Glucocorticoids selectively inhibit the transcription of the interleukin-1β gene and decrease the stability of inter-leukin 1β mRNA. Proc NatlAcad Sci USA 85: 1204–1208

    Article  PubMed  CAS  Google Scholar 

  10. Swantek JL, Cobb MH, Geppert TD (1997) Jun N-terminal kinase/stress-activated protein kinase (JNP/SAPK) is required for lipopolysaccaride stimulation of tumor necrosis factor alpha (TNF-oc) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNP/SAPK. Mol Cell Biol 17: 6274–6282

    PubMed  CAS  Google Scholar 

  11. Siegel JN, June CH (1993) Signal transduction in T-cell activation and tolerance. In: S Gupta, C Griscelli (eds): New concepts in immunodeficiency diseases. John Wiley and Sons., Philadelphia, 85–129

    Google Scholar 

  12. Hanson PI, Shulman H (1992) Neuronal Ca2+/calmodulin-dependent protein kinases. Annu Rev Biochem 61: 559–601

    Article  PubMed  CAS  Google Scholar 

  13. Lou LL, Llyod SJ, Shulman H (1986) Activation of the multifunctional Ca2+/calmodulin protein kinase by autophosphorylation: ATP modulates production of an autonomous enzyme. Proc Natl AcadSci USA83: 9497–9501

    Article  CAS  Google Scholar 

  14. Clipstone NA, Crabtree GR (1992) Identification of calcineurin as a key signaling enzyme in T-lymphocyte activation. Nature 357: 695–697

    Article  PubMed  CAS  Google Scholar 

  15. Emmel EA, Verweij CL, Durand DB, Higgins CM, Lacy E, Crabtree GR (1989) Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science 246: 1617–1620

    Article  PubMed  CAS  Google Scholar 

  16. Cantrell D (1996) T cell antigen receptor signal tranduction pathways. Annu Rev Immunol 14: 259–274

    Article  PubMed  CAS  Google Scholar 

  17. Paliogianni F, Hama N, Balow JE, Valentine MA, Boumpas DT (1995) Glucocorticoid-mediated regulation of protein phosphorylation in primary human T cells: Evidence for induction of phos-phatase activity. J Immunol 1809–1817

    Google Scholar 

  18. Hama N, Paliogianni F, Fessler BJ, Boumpas DT (1995) Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C mediated pathways for cytokine gene transcription in human T cells. J Exp Med 181: 1217–1222

    Article  PubMed  CAS  Google Scholar 

  19. Rao A, Hogan PG (1997) Transcription factors of the NFAT family: Regulation and function. Annu Rev Immunol 15: 707–747

    Article  PubMed  CAS  Google Scholar 

  20. Jain J, Loh C, Rao A (1995) Transcriptional regulation of the interleukin 2 gene. Curr Opin Immunol 7: 333–342

    Article  PubMed  CAS  Google Scholar 

  21. Weiss DL, Hural J, Tara D, Timmerman LA, Henkel G, Brown MA (1996) Nuclear factor of activated T cells is associated with a mast cell interleukin 4 transcription complex. Mol Cell Biol 16: 228–235

    PubMed  CAS  Google Scholar 

  22. Tocci MJ, Matkovich DA, Collier KA, Kwock P, Dumond F, Lin S, Degudicibus S, Siekierka JJ, Chin J, Hutchinson N (1989) The immunosuppressant FK506 selectively inhibits expression of early T activation genes. J Immunol 143: 718–726

    PubMed  CAS  Google Scholar 

  23. Stranick KS, Payvandi F, Zambas DN, Umland SP, Egan RW, Billah MM (1995) Transcription of the murine interleukin 5 gene is regulated by multiple promoter elements. J Biol Chem 270: 20575–20582

    Article  PubMed  CAS  Google Scholar 

  24. Okamoto SI, Makaida N, Yasumoto K, Rice N, Ishikawa Y, Horiguchi H, Murakami S, Matsushima K (1994) The interleukin-8 API and KB-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization. J Biol Chem 269: 8582–8589

    PubMed  CAS  Google Scholar 

  25. Ho N, Gullberg M, Chatila T (1996) Activation protein-1 dependent transcriptional activation of interleukin 2 gene by Ca2+/calmodulin kinase type IV/Gr. J Exp Med 184: 101–112

    Article  PubMed  CAS  Google Scholar 

  26. Paliogianni F, Raptis A, Ahuja SS, Najjar SM, Boumpas DT (1993) Negative transcriptional regulation of human interleukin 2 (IL-2) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT. J Clin Invest 91: 1481–1489

    Article  PubMed  CAS  Google Scholar 

  27. Rooney JW, Hoey T, Glimcher LH (1995) Coordinate and cooperative roles for NFAT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2: 473–483

    Article  PubMed  CAS  Google Scholar 

  28. Cockerill PN, Bert AG, Jenkins F, Ryan GR, Shannon MF, Vadas MA (1995) Human granylocyte-macrophage colony-stimulating factor enhancer function is associated with cooperative interactions between AP-1 and NFATp/c. Mol Cell Biol 15: 2071–2079

    PubMed  CAS  Google Scholar 

  29. Campbell PM, Pimm J, Ramassar V, Halloran PF (1996) Identification of calcium-inducible. Cyclosporine-sensitive elements in the IFN-y promoter that is a potential NFAT binding site Transplantation 61: 933–939

    Article  PubMed  CAS  Google Scholar 

  30. Albert S, Baldwin Jr, (1996) The NF-kB and IkB proteins: New discoveries and insights. Annu Rev Immunol14: 649–681

    Article  Google Scholar 

  31. Schmid R, Liptay S, Betts J, Nabel G (1994) Structural and functional analysis of NF-kB: determinants of DNA binding specificity and protein interaction. J Biol Chem 269: 162–167

    Google Scholar 

  32. Jain J, Burgeon E, Badalian T, Hogan P, Rao A (1995) A similar DNA-binding motif in NFAT family proteins and the Rel homology region. J Biol Chem 270: 4138–4145

    Article  PubMed  CAS  Google Scholar 

  33. Ghosh P, Tan TH, Rice N, Sica A, Young H (1993) The IL-2 CD28-responsive complex contains at least three members of the NF-kB family: c-Rel, p50 and p65. Proc Natl Acad Sci USA 90: 1696–1700

    Article  PubMed  CAS  Google Scholar 

  34. Sun SC, Maggirwar S, Harhaj E (1995) Activation of NF-kB involves the phosphorylation of IkBa at phosphatase 2A-sensitive sites. J Biol Chem 270: 3471–3751

    Article  Google Scholar 

  35. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M (1995) Immunosuppression by gluco-corticoids: Inhibition of NF-kB activity through induction of IkB synthesis. Science 270: 286–289

    Article  PubMed  CAS  Google Scholar 

  36. Scheinman RI, Cogswell PC, Lofquist AK, Baldwin AS (1995) Role of transcriptional activation of IkBoc in mediation of immunosuppression by glucocorticoids. Science 270: 283–286

    Article  PubMed  CAS  Google Scholar 

  37. Ray A, Prefontaine KE (1994) Physical association and functional antagonism between the p65 subunit of transcription factor NF-kB and the glucocorticoid receptor. Proc Natl Acad Sci USA 91: 752–756

    Article  PubMed  CAS  Google Scholar 

  38. Mukaida N, Morita M, Ishikawa Y, Rice N, Okamoto S, Kasahara T, Matsushima K (1994) Novel Mechanism of glucocorticoid-mediated gene repression. Nuclear factor-KB is target for glucocor-ticoid-mediated interleukin 8 gene repression. J Biol Chem 269: 13289–13295

    PubMed  CAS  Google Scholar 

  39. Wissink S, van Heerde EC, vand der Burg B, van der Saag PT (1998) A dual mechanism mediated repression of NF-kappaB activity by glucocorticoids. Mol Endocrinol 12: 355–363

    Article  PubMed  CAS  Google Scholar 

  40. Ullman KS, Northrop JP, Admon A, Crabtree GR (1993) Jun family members are controlled by a calcium-regulated, cyclosporin A-sensitive signalling pathway in activated T lymphocytes. Gene Develop 7: 188–196

    Article  CAS  Google Scholar 

  41. Gruart-Gouilleux V, Engels P, Sullican M (1995) Characterization of the human interleukin-5 gene promoter: involvement of octamer binding sites in the gene promoter activity. Eur J Immunol 25: 1431–1435

    Article  PubMed  CAS  Google Scholar 

  42. Pfeuffer I, Klein-Hebling S, Heifling A, Chuvpilo S, Escher C, Brabletz T, Hentsch B, Schwarzenbach H, Matthias P, Serfling E (1994) Octamer factors exert a dual effect on the IL-2 and IL-4 promoter. J Immunol 153: 5572–5585

    PubMed  CAS  Google Scholar 

  43. Ullman KS, Flanagan WM, Edwards CA, Crabtree GR (1991) Activation of early gene expression in T lymphocytes by Oct-1 and an inducible protein, OAP40. Science 254: 558–561

    Article  PubMed  CAS  Google Scholar 

  44. Paliogianni F, Boumpas DT (1995) Glucocorticoids regulate calcineurin-dependent trans-activating pathways for interleukin-2 gene transcription in human T-lymphocytes. Transplantation 59: 1333–1339

    PubMed  CAS  Google Scholar 

  45. Currant T, Franza BR (1988) Fos and Jun: the AP-1 connection. Cell 55: 395–397

    Article  Google Scholar 

  46. Sundstedt A, Sigvardsson M, Leanderson T, Hedlund G, Kalland T, Dohlsten M (1996) In Vivo anergized CD4+ T cells express perturbed AP-1 and NK-kB transcription factor. Proc Natl Acad Sci USA 93: 979–984

    Article  PubMed  CAS  Google Scholar 

  47. Rao A (1994) NF-ATp: a transcription factor required for coordinate induction of several genes. Immunol Today 15: 274–281

    Article  PubMed  CAS  Google Scholar 

  48. Ray A, LaForge KS, Sehgal PB (1990) On the mechanism for efficient repression of the inter-leukin-6 promoter by glucocorticoids: enhancer, TATA box, and RNA start site (Inr motif) occlusion. Mol Cell Biol10: 5736–5746

    PubMed  CAS  Google Scholar 

  49. Mordacq JC, Linzer DIH (1989) Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression. Gene Develop 3: 760–769

    Article  CAS  Google Scholar 

  50. Akerblom IE, Slater EP, Beato M, Baxter JD, Mellon PL (1988) Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer. Science 241: 350–353

    Article  PubMed  CAS  Google Scholar 

  51. Ray A, Prefontaine KE (1994) Physical association and functional antagonism between the p65 subunits of transcription factor NF-kB and the glucocorticoid receptor. Proc Natl Acad Sci USA 91: 752–756

    Article  PubMed  CAS  Google Scholar 

  52. Kutoh E, Stromstedt PE, Poellinger L (1992) Functional interference between the ubiquitous and constitutive octamer transcription factor 1 (OTF-1) and the glucocorticoid receptor by direct protein-protein interaction involving the homeo subdomain of OCT-1. Mol Cell Biol 12: 4960–4969

    PubMed  CAS  Google Scholar 

  53. Schule R, Rangarajan P, Kliewer S, Ransome LJ, Bolado J, Yank N, Verma IM, Evans RM (1990) Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62: 1217–1226

    Article  PubMed  CAS  Google Scholar 

  54. Yang-Yen HF, Chambard JC, Sun YL, Smeal T, Schmidt TJ, Drouin J, Karin M (1990) Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell 62: 1205–1215

    Article  PubMed  CAS  Google Scholar 

  55. Jonat C, Rahmsdorf HJ, Park KK, Cato AC, Gebel S, Ponta H, Herrlich P (1990) Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62: 1189–1204

    Article  PubMed  CAS  Google Scholar 

  56. Northrop JP, Crabtree GR, Mattila PS (1992) Negative regulation of interleukin 2 transcription by the glucocorticoid receptor. J Exp Med 175: 1235–1245

    Article  PubMed  CAS  Google Scholar 

  57. Ray A, LaForge KS, Sehgal PB (1991) Repressor to activator switch by mutations in the first finger of the glucocorticoid receptor: is direct binding necessary? Proc Natl Acad Sci USA 88: 7086–7090

    Article  PubMed  CAS  Google Scholar 

  58. Nishio Y, Isshiki H, Kishimoto T, Akima S (1993) A nuclear factor for interleukin-6 (NF-IL6) and the glucocorticoid receptor synergistically activate transcription of the rat a 1-acid glycoprotein gene via direct protein-protein interaction. Mol Cell Biol 13: 1854–1862

    PubMed  CAS  Google Scholar 

  59. Prefontaine GG, Lemieu ME, Griffin W, Schild-Poulter C, Pope L, LaCasse E, Walker P, Hache RJ (1988) Recruitment of octamer transcription factors to DNA by glucocorticoid receptor. Mol Cell Biol 18: 3416–3430

    Google Scholar 

  60. Teurich S, Angel P (1995) The glucocorticoid receptor synergizes with Jun homodimers to activate AP-1 regulated promoters lacking GR binding sites. Chem Senses 20: 251–255

    Article  PubMed  CAS  Google Scholar 

  61. Cleveland DW, Yen JJ (1989) Multiple determinants of eucaryotic mRNA stability. New Biol 1: 121–126

    PubMed  CAS  Google Scholar 

  62. Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G (1999) Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 10: 387–398

    Article  PubMed  CAS  Google Scholar 

  63. Bohjanen PR, Petryniac B, June CH, Thomson CB, Lindsten T (1991) An inducible cytoplasmic factor (AU-B) binds selectively to AUUA multimers in the 3’ untranslated region of lymphokine mRNA. Mol Cell Biol 11: 3288–3295

    PubMed  CAS  Google Scholar 

  64. Paliogianni F, Balow JE, Boumpas DT (1997) Glucocorticoids modulate the binding of specific proteins to AU-sequences in the 3’-untranslated region (UTR) of interleukin-2 (IL-2) by activating phosphatases 1 and phosphatase 2. J Alergyl Clin Immunol99: 1954 (Abstract)

    Google Scholar 

  65. Matler JS (1989) Identification of an AUUUA-specific messenger RNA binding. Protein Sci 246: 664–666

    Google Scholar 

  66. Brown EA, Dave HA, Marsh CB, Wewers MD (1996) The combination of endotoxin and dexam-ethasone induces type II interleukin 1 receptor (IL-1 rll) in monocytes: a comparison to interleukin 1 beta (IL-1 beta) and interleukin 1 receptor antagonist (IL-lra). Cytokine 8: 828–836

    Article  PubMed  CAS  Google Scholar 

  67. All M, Vedeckis W (1987) The glucocorticoid receptor protein binds to transfer RNA. Science 235: 467–470

    Article  Google Scholar 

  68. Katz DA, Theodorakis NG, Cleveland DW, Lindsten T, Thomson CB (1993) AU-A and RNA-binding activity distinct from hnRNA Al, is selective for AUUUA repeats and shuttles between the nucleus and the cytoplasm. Nucl Acid Res 22: 238–246

    Article  Google Scholar 

  69. O’Shea JJ (1997) Jaks, STATs, cytokine signal transduction and immunoregulation: Are we there yet? Immunity 7: 1–11

    Article  PubMed  Google Scholar 

  70. Aringer M, Cheng A, Nelson JW, Chen M, Sudarshan C, Zhou Y-J, O’Shea JJ (1999) Janus kinas-es and their role in growth disease. Life Sci 64: 2173–2186

    Article  PubMed  CAS  Google Scholar 

  71. Leonard WJ, O, Shea JJ (1998) JAKs and STATs: Biological implications. Annu Rev Immunol 16: 293–322

    Article  PubMed  CAS  Google Scholar 

  72. Levine SJ, Benfield T, Shelhamer JH (1996) Corticosteroids induce intracellular interleukin-1 receptor antagonist type I expression by a human airway epithelial cell line. Amer J Respir Cell Mol Biol 15: 245–251

    CAS  Google Scholar 

  73. Ho A, Takii T, Goto N, Kito Y, Onozaki K (1997) Role of glucocorticoid in the upregulation of type I interleukin-1 receptor mRNA expression in hepatocytes of endotoxin-administrated mice. J Interferon Cytokine Res 17:413–417

    Article  Google Scholar 

  74. Pietzko Zohlhofer D, Graeve K Fleischer D, Stoyan T, Schooltink H, Rose-John S, Heinrich PC (1993) The hepatic interleukin-6 receptor. Studies on its structure and regulation by phorbol 12-myristate 13-acetate-dexamethasone. J Biol Chem 268: 4250–4258

    Google Scholar 

  75. Snyers L, DeWit L, Content J (1990) Glucocorticoid upregulation of high affinity interleukin 6 receptors on human epithelial cells. Proc NatlAcad Sci USA 87: 2838–2842

    Article  PubMed  CAS  Google Scholar 

  76. Hawrylowicz CM, Guida L, Paleolog E (1994) Dexamethazone upregulates granulocyte-macrophage colony-stimulating factor receptor expression on human monocytes. Immunology 83: 274–280

    PubMed  CAS  Google Scholar 

  77. Novelli F, Di Pierro F, diCelle PF, Bertini S, Affaticati P, Garotta F, Forni G (1994) Environmental signals influencing expression of the IFN-y promotes proliferation or apoptosis. J Immunol 152: 496–504

    PubMed  CAS  Google Scholar 

  78. Strickland RW, Wahl LM, Finbloom DS (1986) Corticosteroids enhance the binding of recombi-nant interferon-y to cultured human monocytes. J Immunol 137: 1577–1580

    PubMed  CAS  Google Scholar 

  79. Michel G, Mirmohammasdadegh A, Olasz E, Jarzeska-Deussen B, Muschen L, Abts HF, Ruzicka T (1997) Demonstration and functional analysis of IL-10 receptors in human epidermal cells: decreased expression in psoriatic skin, down-modulation by IL-8, and up-regulation by an antip-soriatic glucocorticosteroid in normal cultured keratinocytes. J Immunol 159: 6291–6297

    PubMed  CAS  Google Scholar 

  80. Joyce DA, Kloda A Steer JH (1997) Dexamethasone suppresses release of soluble TNF receptors by human monocytes concurrently with TNF-alpha suppression. Immun Cell Biol 75: 345–350

    Article  CAS  Google Scholar 

  81. Levine SJ, Logun C, Chopra DP, Rhim JS, Shelhamer JH (1996) Protein kinase C, interleukin-1 beta, and corticosteroid regulate shedding of the type I, 55 kDa TNF receptor from human airway epithelial cells. Amer J Respir Cell Mol Biol 14: 254–261

    CAS  Google Scholar 

  82. Lamas M, Sanz E, Martin-Parras L, Espel E, Sperizen P, Collins M, Silva AG (1993) Glucocorticoid hormones upregulate interleukin-2 receptor alpha gene expression. Cell Immunol 151:437–450

    Article  PubMed  CAS  Google Scholar 

  83. Boumpas DT, Anastassiou ED, Older SA, Tsokos GC, Nelson DL, Balow JE (1991) Dexamethasone inhibits human interleukin 2 but not interleukin 2 receptor gene expression in vitro at the level of nuclear transcription. J Clin Invest 87: 1739–1747

    Article  PubMed  CAS  Google Scholar 

  84. Wissink S, van Heerde EC, Schmitz ML, Kalkhoven E, van der Burg B, Baeuerle PA, van der Saag PT (1997) Distinct domains of the RelA NK-kappaB subunit are required for negative cross-talk and direct interaction with the glucocorticoid receptor. J Biol Chem 272: 22278–22284

    Article  PubMed  CAS  Google Scholar 

  85. DeBosscher K, Schmitz ML, Vanden Berghe W, Plaisance S, Fiers W, Haegeman G (1997) Glucocorticoid-mediated repression of nuclear factor-kappaB-dependent transcription involves direct interference with transactivation. Proc NatlAcad Sci USA 94: 13504–13509

    Article  CAS  Google Scholar 

  86. Mozo L, Gayo A, Suarez A, Rivas D, Zamorano J, Gutierrez C (1998) Glucocorticoids inhibit IL-4 and mitogen induced IL-4R alpha chain expression by different posttransciptional mechanisms. J Allergy Clin Immunol 102: 968–976

    Article  PubMed  CAS  Google Scholar 

  87. Wright ED, Christodoulopoulos P, Small P, Frenkiel S, Hamid Q (1988) Th-2 type cytokine receptors in allergic rhinitis and in response to topical steroids. Laryngoscope 108: 1528–1533

    Article  Google Scholar 

  88. Stocklin E, Wissler M, Gouilleux F, Groner B (1996) Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383: 726–728

    Article  PubMed  CAS  Google Scholar 

  89. Takade T, Kurachi H, Yamamoto T, Nishio Y, Nakatsuji Y, Morishige Ki Miyake A, Murata Y (1998) Crosstalk between the interleukin-6 (IL-6)-JAK-STAT and the glucocorticoid-nuclear receptor pathway; synergistic activation of IL-6 response elements by IL-6 glucocorticoid. J Endocrinol 159: 323–330

    Article  Google Scholar 

  90. Zhang Z, Jones S, Hagood JS, Fuentes NL, Fuller GM (1997) STAT3 acts as a co-activator of glucocorticoid receptor signaling. J Biol Chem272: 30607–30610

    Article  PubMed  CAS  Google Scholar 

  91. Romagnani S (1991) Human Thl and Th2: doubt no more. Immunol Today 12: 256–257

    Article  PubMed  CAS  Google Scholar 

  92. Wilder RL (1995) Neuroendocrine-immune system interactions and autoimmunity. Annu Rev Immunol 13: 307–338

    Article  PubMed  CAS  Google Scholar 

  93. Arya SK, Wong-Staal F, Gallo RC (1984) Dexamethasone-mediated inhibition of human T-cell growth factor and y-IFN messenger RNA. J Immunol 133: 273–276

    PubMed  CAS  Google Scholar 

  94. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A (1986) Control of cachectin (TNF) synthesis: mechanisms of entotoxin resistance. Science 232: 977–980

    Article  PubMed  CAS  Google Scholar 

  95. Daynes RA, Araneo BA (1989) Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Eur J Immunol 19: 2319–2325

    Article  PubMed  CAS  Google Scholar 

  96. Ramierz FD, Fowell J, Puklavez M, Simmonds S, Mason D (1996) Glucocorticoids promote a Th2 cytokine response by CD4+ T cells in vitro. J Immunol 156: 2406–2412

    Google Scholar 

  97. Blotta MH, Dekruyff RH, Umetsu DT (1997) Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes. J Immunol 158:5589–5595

    PubMed  CAS  Google Scholar 

  98. Hama N, Paliogianni F, Mavrothalassitis G, Yamada H, Boumpas DT (1998) Glucorticoid modulation of cytokine gene transcription opposing effects on pro-inflammatory vs anti-inflammatory cytokine promoters. Arthritis Rheum 41: S194 (Abstract)

    Google Scholar 

  99. Macphee IA, Antoni FA, Mason DW (1989) Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. J Exp Med 169: 431–445

    Article  PubMed  CAS  Google Scholar 

  100. Agarwall SK, Marshall GD (1998) Glucocorticoid-induced type I/type 2 cytokine alterations in humans: a model for stress-related immune disfunction. J Interferon Cytokine Res 18: 1059–1068

    Article  Google Scholar 

  101. Dekruyff RH, Fang Y, Umetsu TD (1998) Corticosteroids enhance the capacity of macrophages to induce Th2 sytokine sythesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 2231–2237

    Google Scholar 

  102. Trinchieri G (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 13: 251–276

    Article  PubMed  CAS  Google Scholar 

  103. Visser J, van Boxel-Dezaire A, Methorst D, Brunt T, de Kloet ER, Nagelkerken L (1998) Differential regulation of interleukin 10 (IL-10) and IL-12 by glucocorticoids in vitro. Blood 91: 4255–4264

    CAS  Google Scholar 

  104. Vieira PL, Kalinski P, Wierenga EA, Kapsenberg ML, de Jong EC (1998) Glucocorticoids inhibit bioactive IL-12p70 production by in vitro generated human dendritic cells without affecting their T cell stimulatory potential. J Immunol 161: 5245–5251

    PubMed  CAS  Google Scholar 

  105. Tamada K, Harada M, Koichiro A, Tieli L, Nomoto K (1998) IL-4 producing NK1.1+ T cells are resistant to glucocorticoid-induced apoptosis: Implications for the Thl/Th2 balance. J. Immunol 161: 1239–1247

    PubMed  CAS  Google Scholar 

  106. Lamberts SWJ, Huizenga ATM, de Lande P, de Jong FH, Koper JW (1996) Clinical aspects of glucocorticoid sensitivity. Steroids 61: 157–160

    Article  PubMed  CAS  Google Scholar 

  107. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsia JJ, Frew AJ, Kay AB (1991) Glucocorticoid resistance in chronic asthma. Glurcocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Amer RevRespirDis 144: 1016–1025

    CAS  Google Scholar 

  108. Morand EF, Jefferiss CM, Dixey J, Mitra D, Goulding NJ (1994) Impaired glucocorticoid induction of mononuclear leukocyte lipocortin-1 in rheumatoid arthritis. Arthritis Rheum 37: 207–211

    Article  PubMed  CAS  Google Scholar 

  109. Miller AH, Pariante CM, Pearce BD (1996) Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistanece and relevance to depression. Adv Exp Med Biol461: 107–116

    Article  Google Scholar 

  110. Kirkham B, Corkill MM, Davison SC, Panayi GS (1991) Response to glucocorticoid treatment in rheumatoid arthritis: in vitro cell mediated immune assay predicts in vivo response. J Rheumatol 18: 30–33

    Google Scholar 

  111. Walker KB, Potter JM, House AK (1985) Variable inhibition of mitogen-induced blastogenesis in human lymphocytes by prednisolone in vitro. Transplant Proc 17: 1676–1678

    PubMed  CAS  Google Scholar 

  112. Langhoff E, laderfoged J, Jacobsen BK (1986) Reciepient lymphocyte sensitivity to methyl prednisolone affects cadaver kidney graft survival. Lancet 2: 1296–1297

    Article  Google Scholar 

  113. Werner S, Thoren M, Gusafasson JA, Bronnegard M (1992) Glucocorticoid receptor abnormalities in fibroblasts from patients with idiopathis resistance of dexamethasone diagnosed when evaluated for adrenocortical disorders. J Clin Endocrinol Metab 75: 1005–1009

    Article  PubMed  CAS  Google Scholar 

  114. Moalli P, Rosen S (1994) Glucocorticoid receptors and resistance to glucocorticoids in hemato-logic malignancies. Leukemia Lymphoma 15: 363–374

    Article  PubMed  CAS  Google Scholar 

  115. Ray DW, Littlewood AC, Clark AJL, Davis JRE, White A (1994) Human small cell lung cancer cell lines expressing the propiomelanocortin gene have aberrant glucocorticoid receptor function. J Clin Invest 93: 1625–1630

    Article  PubMed  CAS  Google Scholar 

  116. Chikanza IC, Panayi GS (1993) The effects of hydrocortisone on in vitro lymphocytes proliferation and interleukin-2 and-4 production in corticosteroid sensitive and resistant subjects. Eur J Clin Invest 23: 845–850

    Article  PubMed  CAS  Google Scholar 

  117. Sher ER, Leung DYM, Surs W, Kam JC, Zieg G, Kamada AK, Szefler SJ (1994) Steroid-resistant asthma. Cellular mechanisms contributing to inadequate response to glucocorticoid therapy. J Clin Invest 93: 33–39

    Article  PubMed  CAS  Google Scholar 

  118. Bamberger CM, Bamberger AM, de Castro Margaret Chrousos GP (1995) Glucocorticoid receptor B, a potential endogenous inhibitor of glucocorticoid action in humans. J Clin Invest 95: 2435–2441

    Article  PubMed  CAS  Google Scholar 

  119. Norbiato G, Bevilacqua M, Vago T (1992) Cortisol resistance in acquired immunodeficiency syndrome. J Clin Endocrinol Metab 14: 608–613

    Article  Google Scholar 

  120. Leung DYM, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, Chrousos GP, Klemm DJ (1997) Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta. J Exp Med 186: 1567–1574

    Article  PubMed  CAS  Google Scholar 

  121. Adcock IM, Lane SJ, Brown CR, Peters MJ, Lee TH, Barnes PJ (1995) Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. J Immunol 154: 3500–3505

    PubMed  CAS  Google Scholar 

  122. Almawi WY, Lipman ML, Stevens AC, Zanker B, Hadro ET, Strom TB (1991) Abrogation of glucocorticoid mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6 and IFN-gamma. J Immunol 146: 3523–3537

    PubMed  CAS  Google Scholar 

  123. Kam JC, Szefler SJ, Surs W, Sher ER, Leung DYM (1993) Combination IL-2 and IL-4 reduced glucocorticoid receptor-binding affinity and T cell response to glucocorticoids1. J Immunol 151: 3460

    PubMed  CAS  Google Scholar 

  124. Braack A, Tieener HL, Younge BR, Kaltschmidt C, Weyand CM, Goronzy (1997) Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras. J Clin Invest 99: 28442–28450

    Article  Google Scholar 

  125. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, Gronemeyer H, Resche-Rigon M (1997) Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepres-sion exhibit antiinflammatory activity in vivo. Mol Endocrinol 11: 1245–1255

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, University of Patra, Patra, 26224, Greece

    Fotini Paliogianni

  2. National Institutes of Health, Bethesda, Maryland, 20892, USA

    Dimitrios T. Boumpas

  3. Division of Rheumatology Clinical Immunology and Allergy, University of Crete, Heraklion, 71300, Greece

    Dimitrios T. Boumpas

Authors
  1. Fotini Paliogianni
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  2. Dimitrios T. Boumpas
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  1. Dept of Biochemical Pharmacology William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary, University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Nicolas J. Goulding  & Rod J. Flower  & 

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© 2001 Springer Basel AG

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Paliogianni, F., Boumpas, D.T. (2001). Molecular and cellular aspects of cytokine regulation by glucocorticoids. In: Goulding, N.J., Flower, R.J. (eds) Glucocorticoids. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8348-1_5

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  • DOI: https://doi.org/10.1007/978-3-0348-8348-1_5

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9528-6

  • Online ISBN: 978-3-0348-8348-1

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