Skip to main content
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1998;7(3):183–193. doi: 10.1080/09629359891126

Topical glucocorticoids and the skin--mechanisms of action: an update.

A Ahluwalia 1
PMCID: PMC1781846  PMID: 9705606

Abstract

The topical glucocorticoids (GCs) represent the treatment of choice for many types of inflammatory dermatoses. Despite the extensive use of this class of drugs as first line therapy the mechanism of their action is uncertain. It is clear that the multiplicity of actions of the topical GCs is an important facet of their scope in the treatment of dermal disorders. The aim of this update is to review past and current theories regarding how these agents might work. Current understanding of the molecular mechanisms of GC action has advanced significantly over the past decade with the realisation that multiple systems are responsible for transduction of GC effects at a molecular level. The two primary modes of action are via interaction directly with DNA or indirectly through modulation of specific transcription factors: the endpoint in both cases being modulation of specific protein synthesis. Both of these mechanisms will be discussed. In particular this review will concentrate on the possibility that a GC-inducible protein, termed lipocortin 1, may have a significant role to play in the anti-inflammatory actions of these drugs. Additionally it has become apparent that several inflammatory enzymes induced in inflammation are sites of inhibitory action of the GCs, and the possibility that this occurs in the skin will be discussed paying particular attention to the inducible phospholipase A2, nitric oxide synthase and cyclooxygenase systems.

Full Text

The Full Text of this article is available as a PDF (314.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adcock I. M., Brown C. R., Barnes P. J. Tumour necrosis factor alpha causes retention of activated glucocorticoid receptor within the cytoplasm of A549 cells. Biochem Biophys Res Commun. 1996 Aug 14;225(2):545–550. doi: 10.1006/bbrc.1996.1209. [DOI] [PubMed] [Google Scholar]
  2. Ahluwalia A., Mohamed R. W., Flower R. J. Induction of lipocortin 1 by topical steroid in rat skin. Biochem Pharmacol. 1994 Oct 18;48(8):1647–1654. doi: 10.1016/0006-2952(94)90210-0. [DOI] [PubMed] [Google Scholar]
  3. Ahluwalia A., Newbold P., Brain S. D., Flower R. J. Topical glucocorticoids inhibit neurogenic inflammation: involvement of lipocortin 1. Eur J Pharmacol. 1995 Sep 5;283(1-3):193–198. doi: 10.1016/0014-2999(95)00350-t. [DOI] [PubMed] [Google Scholar]
  4. Ahluwalia A., Perretti M. Anti-inflammatory effect of prostanoids in mouse and rat skin: evidence for a role of EP3-receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1526–1531. [PubMed] [Google Scholar]
  5. Akner G., Wikström A. C., Gustafsson J. A. Subcellular distribution of the glucocorticoid receptor and evidence for its association with microtubules. J Steroid Biochem Mol Biol. 1995 Jan;52(1):1–16. doi: 10.1016/0960-0760(94)00155-f. [DOI] [PubMed] [Google Scholar]
  6. Alam R., Dejarnatt A., Stafford S., Forsythe P. A., Kumar D., Grant J. A. Selective inhibition of the cutaneous late but not immediate allergic response to antigens by misoprostol, a PGE analog. Results of a double-blind, placebo-controlled randomized study. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):1066–1070. doi: 10.1164/ajrccm/148.4_Pt_1.1066. [DOI] [PubMed] [Google Scholar]
  7. Andersson M., Pipkorn U. Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids. J Allergy Clin Immunol. 1987 Feb;79(2):345–349. doi: 10.1016/0091-6749(87)90153-9. [DOI] [PubMed] [Google Scholar]
  8. Appleton I., Tomlinson A., Willoughby D. A. Induction of cyclo-oxygenase and nitric oxide synthase in inflammation. Adv Pharmacol. 1996;35:27–78. doi: 10.1016/s1054-3589(08)60274-4. [DOI] [PubMed] [Google Scholar]
  9. Auphan N., DiDonato J. A., Rosette C., Helmberg A., Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science. 1995 Oct 13;270(5234):286–290. doi: 10.1126/science.270.5234.286. [DOI] [PubMed] [Google Scholar]
  10. Baeuerle P. A., Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988 Oct 28;242(4878):540–546. doi: 10.1126/science.3140380. [DOI] [PubMed] [Google Scholar]
  11. Baker J. R., Christian R. A., Simpson P., White A. M. The binding of topically applied glucocorticoids to rat skin. Br J Dermatol. 1977 Feb;96(2):171–178. doi: 10.1111/j.1365-2133.1977.tb12540.x. [DOI] [PubMed] [Google Scholar]
  12. Baldwin A. S., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. doi: 10.1146/annurev.immunol.14.1.649. [DOI] [PubMed] [Google Scholar]
  13. Bastian B. C., Sellert C., Seekamp A., Römisch J., Pâques E. P., Bröcker E. B. Inhibition of human skin phospholipase A2 by "lipocortins" is an indirect effect of substrate/lipocortin interaction. J Invest Dermatol. 1993 Sep;101(3):359–363. doi: 10.1111/1523-1747.ep12365541. [DOI] [PubMed] [Google Scholar]
  14. Baxter D. L., Stoughton R. B. Mitotic index of psoriatic lesions treated with anthralin, glucocorticosteriod and occlusion only. J Invest Dermatol. 1970 May;54(5):410–412. doi: 10.1111/1523-1747.ep12259209. [DOI] [PubMed] [Google Scholar]
  15. Bertini R., Bianchi M., Ghezzi P. Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J Exp Med. 1988 May 1;167(5):1708–1712. doi: 10.1084/jem.167.5.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Blackwell G. J., Flower R. J., Nijkamp F. P., Vane J. R. Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids. Br J Pharmacol. 1978 Jan;62(1):79–89. doi: 10.1111/j.1476-5381.1978.tb07009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Brann D. W., Hendry L. B., Mahesh V. B. Emerging diversities in the mechanism of action of steroid hormones. J Steroid Biochem Mol Biol. 1995 Feb;52(2):113–133. doi: 10.1016/0960-0760(94)00160-n. [DOI] [PubMed] [Google Scholar]
  18. Brink M., Humbel B. M., De Kloet E. R., Van Driel R. The unliganded glucocorticoid receptor is localized in the nucleus, not in the cytoplasm. Endocrinology. 1992 Jun;130(6):3575–3581. doi: 10.1210/endo.130.6.1597154. [DOI] [PubMed] [Google Scholar]
  19. Brostjan C., Anrather J., Csizmadia V., Stroka D., Soares M., Bach F. H., Winkler H. Glucocorticoid-mediated repression of NFkappaB activity in endothelial cells does not involve induction of IkappaBalpha synthesis. J Biol Chem. 1996 Aug 9;271(32):19612–19616. doi: 10.1074/jbc.271.32.19612. [DOI] [PubMed] [Google Scholar]
  20. Browning J. L., Ward M. P., Wallner B. P., Pepinsky R. B. Studies on the structural properties of lipocortin-1 and the regulation of its synthesis by steroids. Prog Clin Biol Res. 1990;349:27–45. [PubMed] [Google Scholar]
  21. Camp R. D., Fincham N. J., Cunningham F. M., Greaves M. W., Morris J., Chu A. Psoriatic skin lesions contain biologically active amounts of an interleukin 1-like compound. J Immunol. 1986 Dec 1;137(11):3469–3474. [PubMed] [Google Scholar]
  22. Chu A. C., Munn S. Fluticasone propionate in the treatment of inflammatory dermatoses. Br J Clin Pract. 1995 May-Jun;49(3):131–133. [PubMed] [Google Scholar]
  23. Croxtal J. D., Newman S. P., Choudhury Q., Flower R. J. The concerted regulation of cPLA2, COX2, and lipocortin 1 expression by IL-1beta in A549 cells. Biochem Biophys Res Commun. 1996 Mar 27;220(3):491–495. doi: 10.1006/bbrc.1996.0432. [DOI] [PubMed] [Google Scholar]
  24. Croxtall J. D., Flower R. J. Antisense oligonucleotides to human lipocortin-1 inhibit glucocorticoid-induced inhibition of A549 cell growth and eicosanoid release. Biochem Pharmacol. 1994 Nov 1;48(9):1729–1734. doi: 10.1016/0006-2952(94)90458-8. [DOI] [PubMed] [Google Scholar]
  25. Croxtall J. D., Flower R. J. Lipocortin 1 mediates dexamethasone-induced growth arrest of the A549 lung adenocarcinoma cell line. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3571–3575. doi: 10.1073/pnas.89.8.3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Danon A., Assouline G. Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Nature. 1978 Jun 15;273(5663):552–554. doi: 10.1038/273552a0. [DOI] [PubMed] [Google Scholar]
  27. Davidson F. F., Dennis E. A., Powell M., Glenney J. R., Jr Inhibition of phospholipase A2 by "lipocortins" and calpactins. An effect of binding to substrate phospholipids. J Biol Chem. 1987 Feb 5;262(4):1698–1705. [PubMed] [Google Scholar]
  28. DeWitt D. L. Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochim Biophys Acta. 1991 May 8;1083(2):121–134. doi: 10.1016/0005-2760(91)90032-d. [DOI] [PubMed] [Google Scholar]
  29. Di Rosa M., Flower R. J., Hirata F., Parente L., Russo-Marie F. Anti-phospholipase proteins. Prostaglandins. 1984 Oct;28(4):441–442. doi: 10.1016/0090-6980(84)90232-6. [DOI] [PubMed] [Google Scholar]
  30. Duval D., Freyss-Beguin M. Glucocorticoids and prostaglandin synthesis: we cannot see the wood for the trees. Prostaglandins Leukot Essent Fatty Acids. 1992 Feb;45(2):85–112. doi: 10.1016/0952-3278(92)90225-8. [DOI] [PubMed] [Google Scholar]
  31. Eklund K. K., Humphries D. E., Xia Z., Ghildyal N., Friend D. S., Gross V., Stevens R. L. Glucocorticoids inhibit the cytokine-induced proliferation of mast cells, the high affinity IgE receptor-mediated expression of TNF-alpha, and the IL-10-induced expression of chymases. J Immunol. 1997 May 1;158(9):4373–4380. [PubMed] [Google Scholar]
  32. Epstein E. H., Jr, Bonifas J. M. Glucocorticoid receptors of normal human epidermis. J Invest Dermatol. 1982 Feb;78(2):144–146. doi: 10.1111/1523-1747.ep12506283. [DOI] [PubMed] [Google Scholar]
  33. Epstein E. H., Jr, Munderloh N. H. Glucocorticoid receptors of mouse epidermis and dermis. Endocrinology. 1981 Feb;108(2):703–711. doi: 10.1210/endo-108-2-703. [DOI] [PubMed] [Google Scholar]
  34. Fava R. A., McKanna J., Cohen S. Lipocortin I (p35) is abundant in a restricted number of differentiated cell types in adult organs. J Cell Physiol. 1989 Nov;141(2):284–293. doi: 10.1002/jcp.1041410209. [DOI] [PubMed] [Google Scholar]
  35. Fisher L. B., Maibach H. I. The effect of corticosteroids on human epidermal mitotic activity. Arch Dermatol. 1971 Jan;103(1):39–44. [PubMed] [Google Scholar]
  36. Fisher L. B., Maibach H. I. The effect of corticosteroids on human epidermal mitotic activity. Arch Dermatol. 1971 Jan;103(1):39–44. [PubMed] [Google Scholar]
  37. Flower R. J., Blackwell G. J. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature. 1979 Mar 29;278(5703):456–459. doi: 10.1038/278456a0. [DOI] [PubMed] [Google Scholar]
  38. Flower R. J., Parente L., Persico P., Salmon J. A. A comparison of the acute inflammatory response in adrenalectomised and sham-operated rats. Br J Pharmacol. 1986 Jan;87(1):57–62. doi: 10.1111/j.1476-5381.1986.tb10156.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Forster S., Ilderton E., Norris J. F., Summerly R., Yardley H. J. Characterization and activity of phospholipase A2 in normal human epidermis and in lesion-free epidermis of patients with psoriasis or eczema. Br J Dermatol. 1985 Feb;112(2):135–147. doi: 10.1111/j.1365-2133.1985.tb00077.x. [DOI] [PubMed] [Google Scholar]
  40. Gaillard R. C., Poffet D., Riondel A. M., Saurat J. H. RU 486 inhibits peripheral effects of glucocorticoids in humans. J Clin Endocrinol Metab. 1985 Dec;61(6):1009–1011. doi: 10.1210/jcem-61-6-1009. [DOI] [PubMed] [Google Scholar]
  41. Galli S. J. New concepts about the mast cell. N Engl J Med. 1993 Jan 28;328(4):257–265. doi: 10.1056/NEJM199301283280408. [DOI] [PubMed] [Google Scholar]
  42. Gasc J. M., Delahaye F., Baulieu E. E. Compared intracellular localization of the glucocorticosteroid and progesterone receptors: an immunocytochemical study. Exp Cell Res. 1989 Apr;181(2):492–504. doi: 10.1016/0014-4827(89)90106-7. [DOI] [PubMed] [Google Scholar]
  43. Goldsmith P. C., Leslie T. A., Hayes N. A., Levell N. J., Dowd P. M., Foreman J. C. Inhibitors of nitric oxide synthase in human skin. J Invest Dermatol. 1996 Jan;106(1):113–118. doi: 10.1111/1523-1747.ep12328204. [DOI] [PubMed] [Google Scholar]
  44. Gorski J., Toft D., Shyamala G., Smith D., Notides A. Hormone receptors: studies on the interaction of estrogen with the uterus. Recent Prog Horm Res. 1968;24:45–80. doi: 10.1016/b978-1-4831-9827-9.50008-3. [DOI] [PubMed] [Google Scholar]
  45. Greaves M. W., Plummer V. M. Glucocorticoid inhibition of antigen-evoked histamine release from human skin. Immunology. 1974 Sep;27(3):359–364. [PMC free article] [PubMed] [Google Scholar]
  46. Grossman R. M., Krueger J., Yourish D., Granelli-Piperno A., Murphy D. P., May L. T., Kupper T. S., Sehgal P. B., Gottlieb A. B. Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6367–6371. doi: 10.1073/pnas.86.16.6367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Hammarström S., Hamberg M., Duell E. A., Stawiski M. A., Anderson T. F., Voorhees J. J. Glucocorticoid in inflammatory proliferative skin disease reduces arachidonic and hydroxyeicosatetraenoic acids. Science. 1977 Sep 2;197(4307):994–996. doi: 10.1126/science.887938. [DOI] [PubMed] [Google Scholar]
  48. Han J. W., Sadowski H., Young D. A., Macara I. G. Persistent induction of cyclooxygenase in p60v-src-transformed 3T3 fibroblasts. Proc Natl Acad Sci U S A. 1990 May;87(9):3373–3377. doi: 10.1073/pnas.87.9.3373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Herschman H. R. Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metastasis Rev. 1994 Dec;13(3-4):241–256. doi: 10.1007/BF00666095. [DOI] [PubMed] [Google Scholar]
  50. Hla T., Ristimäki A., Appleby S., Barriocanal J. G. Cyclooxygenase gene expression in inflammation and angiogenesis. Ann N Y Acad Sci. 1993 Nov 30;696:197–204. doi: 10.1111/j.1749-6632.1993.tb17152.x. [DOI] [PubMed] [Google Scholar]
  51. Hong S. L., Levine L. Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc Natl Acad Sci U S A. 1976 May;73(5):1730–1734. doi: 10.1073/pnas.73.5.1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Ikai K., Shimizu K., Ando Y., Furukawa F., Imamura S., Kannagi R. Immunohistochemical localization of lipocortins in normal and psoriatic human skin. Arch Dermatol Res. 1993;285(5):296–299. doi: 10.1007/BF00371600. [DOI] [PubMed] [Google Scholar]
  53. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  54. Kang R. Y., Freire-Moar J., Sigal E., Chu C. Q. Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. Br J Rheumatol. 1996 Aug;35(8):711–718. doi: 10.1093/rheumatology/35.8.711. [DOI] [PubMed] [Google Scholar]
  55. Kim K. M., Kim D. K., Park Y. M., Kim C. K., Na D. S. Annexin-I inhibits phospholipase A2 by specific interaction, not by substrate depletion. FEBS Lett. 1994 May 2;343(3):251–255. doi: 10.1016/0014-5793(94)80566-0. [DOI] [PubMed] [Google Scholar]
  56. Kitajima Y., Owada M. K., Mitsui H., Yaoita H. Lipocortin I (annexin I) is preferentially localized on the plasma membrane in keratinocytes of psoriatic lesional epidermis as shown by immunofluorescence microscopy. J Invest Dermatol. 1991 Dec;97(6):1032–1038. doi: 10.1111/1523-1747.ep12492494. [DOI] [PubMed] [Google Scholar]
  57. Kolb-Bachofen V., Fehsel K., Michel G., Ruzicka T. Epidermal keratinocyte expression of inducible nitric oxide synthase in skin lesions of psoriasis vulgaris. Lancet. 1994 Jul 9;344(8915):139–139. doi: 10.1016/s0140-6736(94)91328-5. [DOI] [PubMed] [Google Scholar]
  58. Kujubu D. A., Herschman H. R. Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene. J Biol Chem. 1992 Apr 25;267(12):7991–7994. [PubMed] [Google Scholar]
  59. Lavker R. M., Schechter N. M. Cutaneous mast cell depletion results from topical corticosteroid usage. J Immunol. 1985 Oct;135(4):2368–2373. [PubMed] [Google Scholar]
  60. Lawrence E., Brain S. D. Responses to endothelins in the rat cutaneous microvasculature: a modulatory role of locally-produced nitric oxide. Br J Pharmacol. 1992 Jul;106(3):733–738. doi: 10.1111/j.1476-5381.1992.tb14402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Lee S. W., Tsou A. P., Chan H., Thomas J., Petrie K., Eugui E. M., Allison A. C. Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1204–1208. doi: 10.1073/pnas.85.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Lyons C. R. The role of nitric oxide in inflammation. Adv Immunol. 1995;60:323–371. doi: 10.1016/s0065-2776(08)60589-1. [DOI] [PubMed] [Google Scholar]
  63. Marks R., Barlow J. W., Funder J. W. Steroid-induced vasoconstriction: glucocorticoid antagonist studies. J Clin Endocrinol Metab. 1982 May;54(5):1075–1077. doi: 10.1210/jcem-54-5-1075. [DOI] [PubMed] [Google Scholar]
  64. Masferrer J. L., Reddy S. T., Zweifel B. S., Seibert K., Needleman P., Gilbert R. S., Herschman H. R. In vivo glucocorticoids regulate cyclooxygenase-2 but not cyclooxygenase-1 in peritoneal macrophages. J Pharmacol Exp Ther. 1994 Sep;270(3):1340–1344. [PubMed] [Google Scholar]
  65. Masferrer J. L., Seibert K., Zweifel B., Needleman P. Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3917–3921. doi: 10.1073/pnas.89.9.3917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Masferrer J. L., Zweifel B. S., Seibert K., Needleman P. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest. 1990 Oct;86(4):1375–1379. doi: 10.1172/JCI114850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Mukaida N., Gussella G. L., Kasahara T., Ko Y., Zachariae C. O., Kawai T., Matsushima K. Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line. Immunology. 1992 Apr;75(4):674–679. [PMC free article] [PubMed] [Google Scholar]
  68. Mukaida N., Morita M., Ishikawa Y., Rice N., Okamoto S., Kasahara T., Matsushima K. Novel mechanism of glucocorticoid-mediated gene repression. Nuclear factor-kappa B is target for glucocorticoid-mediated interleukin 8 gene repression. J Biol Chem. 1994 May 6;269(18):13289–13295. [PubMed] [Google Scholar]
  69. NEWMAN B. A., FELDMAN F. F. Effects of topical cortisone on chronic discoid lupus erythematosus and necrobiosis lipoidica diabeticorum. J Invest Dermatol. 1951 Jul;17(1):3–6. doi: 10.1038/jid.1951.54. [DOI] [PubMed] [Google Scholar]
  70. Noon J. P., Evans C. E., Haynes W. G., Webb D. J., Walker B. R. A comparison of techniques to assess skin blanching following the topical application of glucocorticoids. Br J Dermatol. 1996 May;134(5):837–842. [PubMed] [Google Scholar]
  71. Norris J. F., Ilderton E., Yardley H. J., Summerly R., Forster S. Utilization of epidermal phospholipase A2 inhibition to monitor topical steroid action. Br J Dermatol. 1984 Jul;111 (Suppl 27):195–203. doi: 10.1111/j.1365-2133.1984.tb15605.x. [DOI] [PubMed] [Google Scholar]
  72. Paliogianni F., Raptis A., Ahuja S. S., Najjar S. M., Boumpas D. T. 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. 1993 Apr;91(4):1481–1489. doi: 10.1172/JCI116353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Perretti M., Flower R. J. Cytokines, glucocorticoids and lipocortins in the control of neutrophil migration. Pharmacol Res. 1994 Jul;30(1):53–59. doi: 10.1016/1043-6618(94)80087-1. [DOI] [PubMed] [Google Scholar]
  74. Perretti M. Lipocortin-derived peptides. Biochem Pharmacol. 1994 Mar 15;47(6):931–938. doi: 10.1016/0006-2952(94)90402-2. [DOI] [PubMed] [Google Scholar]
  75. Picard D., Salser S. J., Yamamoto K. R. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell. 1988 Sep 23;54(7):1073–1080. doi: 10.1016/0092-8674(88)90122-5. [DOI] [PubMed] [Google Scholar]
  76. Pipkorn U., Hammarlund A., Enerbäck L. Prolonged treatment with topical glucocorticoids results in an inhibition of the allergen-induced weal-and-flare response and a reduction in skin mast cell numbers and histamine content. Clin Exp Allergy. 1989 Jan;19(1):19–25. doi: 10.1111/j.1365-2222.1989.tb02338.x. [DOI] [PubMed] [Google Scholar]
  77. Ponec M., Kempenaar J. A., De Kloet E. R. Corticoids and cultured human epidermal keratinocytes: specific intracellular binding and clinical efficacy. J Invest Dermatol. 1981 Mar;76(3):211–214. doi: 10.1111/1523-1747.ep12525761. [DOI] [PubMed] [Google Scholar]
  78. Pratt W. B. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem. 1993 Oct 15;268(29):21455–21458. [PubMed] [Google Scholar]
  79. Ray A., LaForge K. S., Sehgal P. B. On the mechanism for efficient repression of the interleukin-6 promoter by glucocorticoids: enhancer, TATA box, and RNA start site (Inr motif) occlusion. Mol Cell Biol. 1990 Nov;10(11):5736–5746. doi: 10.1128/mcb.10.11.5736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Ray A., Zhang D. H., Siegel M. D., Ray P. Regulation of interleukin-6 gene expression by steroids. Ann N Y Acad Sci. 1995 Jul 21;762:79–88. doi: 10.1111/j.1749-6632.1995.tb32316.x. [DOI] [PubMed] [Google Scholar]
  81. Raynal P., Pollard H. B. Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins. Biochim Biophys Acta. 1994 Apr 5;1197(1):63–93. doi: 10.1016/0304-4157(94)90019-1. [DOI] [PubMed] [Google Scholar]
  82. Raz A., Wyche A., Needleman P. Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1657–1661. doi: 10.1073/pnas.86.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Ristimäki A., Narko K., Hla T. Down-regulation of cytokine-induced cyclo-oxygenase-2 transcript isoforms by dexamethasone: evidence for post-transcriptional regulation. Biochem J. 1996 Aug 15;318(Pt 1):325–331. doi: 10.1042/bj3180325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Rowe A., Farrell A. M., Bunker C. B. Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses. Br J Dermatol. 1997 Jan;136(1):18–23. [PubMed] [Google Scholar]
  85. Rupprecht R., Reul J. M., van Steensel B., Spengler D., Söder M., Berning B., Holsboer F., Damm K. Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol. 1993 Oct 15;247(2):145–154. doi: 10.1016/0922-4106(93)90072-h. [DOI] [PubMed] [Google Scholar]
  86. SULZBERGER M. B., WITTEN V. H. The effect of topically applied compound F in selected dermatoses. J Invest Dermatol. 1952 Aug;19(2):101–102. doi: 10.1038/jid.1952.72. [DOI] [PubMed] [Google Scholar]
  87. Samet J. M., Fasano M. B., Fonteh A. N., Chilton F. H. Selective induction of prostaglandin G/H synthase I by stem cell factor and dexamethasone in mast cells. J Biol Chem. 1995 Apr 7;270(14):8044–8049. doi: 10.1074/jbc.270.14.8044. [DOI] [PubMed] [Google Scholar]
  88. Sanchez E. R., Meshinchi S., Tienrungroj W., Schlesinger M. J., Toft D. O., Pratt W. B. Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor. J Biol Chem. 1987 May 25;262(15):6986–6991. [PubMed] [Google Scholar]
  89. Schalkwijk C. G., Vervoordeldonk M., Pfeilschifter J., van den Bosch H. Interleukin-1 beta-induced cytosolic phospholipase A2 activity and protein synthesis is blocked by dexamethasone in rat mesangial cells. FEBS Lett. 1993 Nov 1;333(3):339–343. doi: 10.1016/0014-5793(93)80683-l. [DOI] [PubMed] [Google Scholar]
  90. Scheinman R. I., Cogswell P. C., Lofquist A. K., Baldwin A. S., Jr Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science. 1995 Oct 13;270(5234):283–286. doi: 10.1126/science.270.5234.283. [DOI] [PubMed] [Google Scholar]
  91. Serres M., Comera C., Schmitt D. Annexin 1 regulation in human epidermal cells. Cell Mol Biol (Noisy-le-grand) 1994 Jul;40(5):701–706. [PubMed] [Google Scholar]
  92. Serres M., Viac J., Comera C., Schmitt D. Expression of annexin I in freshly isolated human epidermal cells and in cultured keratinocytes. Arch Dermatol Res. 1994;286(5):268–272. doi: 10.1007/BF00387599. [DOI] [PubMed] [Google Scholar]
  93. Serres M., Viac J., Schmitt D. Glucocorticoid receptor localization in human epidermal cells. Arch Dermatol Res. 1996 Mar;288(3):140–146. doi: 10.1007/BF02505823. [DOI] [PubMed] [Google Scholar]
  94. Smith D. F., Toft D. O. Steroid receptors and their associated proteins. Mol Endocrinol. 1993 Jan;7(1):4–11. doi: 10.1210/mend.7.1.8446107. [DOI] [PubMed] [Google Scholar]
  95. Szapary D., Barber T., Dwyer N. K., Blanchette-Mackie E. J., Simons S. S., Jr Microtubules are not required for glucocorticoid receptor mediated gene induction. J Steroid Biochem Mol Biol. 1994 Nov;51(3-4):143–148. doi: 10.1016/0960-0760(94)90087-6. [DOI] [PubMed] [Google Scholar]
  96. Van de Kerkhof P. C., Van Erp P. E. The role of epidermal proliferation in the pathogenesis of psoriasis. Skin Pharmacol. 1996;9(6):343–354. doi: 10.1159/000211445. [DOI] [PubMed] [Google Scholar]
  97. Vishwanath B. S., Frey F. J., Bradbury M., Dallman M. F., Frey B. M. Adrenalectomy decreases lipocortin-I messenger ribonucleic acid and tissue protein content in rats. Endocrinology. 1992 Feb;130(2):585–591. doi: 10.1210/endo.130.2.1531128. [DOI] [PubMed] [Google Scholar]
  98. Voorhees J. J., Duell E. A., Anderson T. F., Stawiski M. A., Hammarström S., Hamberg M. Pharmacological effects of glucocorticoid on arachidonic acid content of lesions of psoriasis. Adv Prostaglandin Thromboxane Res. 1978;3:175–181. [PubMed] [Google Scholar]
  99. Walker B. R., Williams B. C. Corticosteroids and vascular tone: mapping the messenger maze. Clin Sci (Lond) 1992 Jun;82(6):597–605. doi: 10.1042/cs0820597. [DOI] [PubMed] [Google Scholar]
  100. Warren J. B. Nitric oxide and human skin blood flow responses to acetylcholine and ultraviolet light. FASEB J. 1994 Feb;8(2):247–251. doi: 10.1096/fasebj.8.2.7509761. [DOI] [PubMed] [Google Scholar]
  101. Weber C., Erl W., Pietsch A., Weber P. C. Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells. Circulation. 1995 Apr 1;91(7):1914–1917. doi: 10.1161/01.cir.91.7.1914. [DOI] [PubMed] [Google Scholar]
  102. Whitmarsh A. J., Davis R. J. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med (Berl) 1996 Oct;74(10):589–607. doi: 10.1007/s001090050063. [DOI] [PubMed] [Google Scholar]
  103. Zhang G., Zhang L., Duff G. W. A negative regulatory region containing a glucocorticosteroid response element (nGRE) in the human interleukin-1beta gene. DNA Cell Biol. 1997 Feb;16(2):145–152. doi: 10.1089/dna.1997.16.145. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES