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Corticosteroids induce proliferation but do not influence TNF- or IL-1Β-induced ICAM-1 expression of human dermal microvascular endothelial cells in vitro

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Abstract

The effects of hydrocortisone, dexamethasone, betamethasone 17-valerate and clobetasol propionate at concentrations of 10−5–10−12 M on the proliferation of human dermal microvascular endothelial cells (HDMEC) were studied in vitro. In addition, confluent HDMEC were treated with TNF (1000 U/ml) or IL-1Β (1000 U/ml) alone or in combination with the corticosteroids (10−5 M, 10−6 M) for 24 h, and cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) was assessed by immunocytochemistry. Controls were treated either with growth medium or with the corticosteroids alone. All tested corticosteroids stimulated HDMEC growth after 4 and 6 days of treatment in a dose-dependent manner, as assessed by 3H-thymidine incorporation and the 4-methyl-umbelliferyl heptanoate (MUH) assay. The minimal effective concentration was 10−9 M for hydrocortisone, 10−10 M for dexamethasone and betamethasone, and 10−12 M for clobetasol. In untreated and in corticosteroid-treated cultures, less than 5% of the cells expressed ICAM-1. TNF and IL-1Β were strong inducers of ICAM-1 expression on 74% and 82% of the cells, respectively. None of the tested corticosteroids significantly influenced cytokine-induced ICAM-1 expression, suggesting that the anti-inflammatory effects of corticosteroids are not related to ICAM-1 modulation on HDMEC.

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References

  1. Barker JNWN, Allen MH, MacDonald DM (1989) The effect of in vivo interferon-gamma on the distribution of LFA-1 and ICAM-1 in normal human skin. J Invest Dermatol 93: 439–442

    Google Scholar 

  2. Bateman DN (1989) Clinical pharmacology of topical steroids. In: Greaves MW, Shuster S (eds) Pharmacology of the skin II. Springer, Berlin Heidelberg New York, pp. 239–249

    Google Scholar 

  3. Cordell JL, Falini B, Erber WN, Ghosh A, Zainalabideen A, MacDonald S, Pulford KAF, Stein H, Mason DY (1984) Immunoenzymatic labelling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32: 219–229

    Google Scholar 

  4. Cotran RS, Gimbrone Jr MA, Bevilacqua MP, Mendrick DL, Pober JS (1986) Induction and detection of human endothelial antigen in vivo. J Exp Med 164: 661–666

    Google Scholar 

  5. Delforno C, Holt PJA, Marks R (1978) Corticosteroid effects on epidermal cell size. Br J Dermatol 98: 619–623

    Google Scholar 

  6. Detmar M, Orfanos CE (1990) Tumor necrosis factor-alpha inhibits cell proliferation and induces class II antigens and cell adhesion molecules in cultured normal human keratinocytes in vitro. Arch Dermatol Res 282: 238–245

    Google Scholar 

  7. Detmar M, Mayer-da-Silva A, Stadler R, Orfanos CE (1989) Effects of azelaic acid on proliferation and ultrastructure of mouse keratinocytes in vitro. J Invest Dermatol 93: 70–74

    Google Scholar 

  8. Detmar M, Imcke E, Ruszczak Zb, Orfanos CE (1990) Effects of recombinant tumor necrosis factor-alpha on cultured microvascular endothelial cells derived from human dermis. J Invest Dermatol 95: 219S-222S

    Google Scholar 

  9. Detmar M, Tenorio S, Hettmannsperger U, Ruszczak Zb, Orfanos CE (1992) Cytokine regulation of proliferation and ICAM-1 expression of human dermal microvascular endothelial cells in vitro. J Invest Dermatol 98: 147–153

    Google Scholar 

  10. Didinsky JB, Rheinwald JG (1981) Failure of hydrocortisone or growth factors to influence the senescence of fibroblasts in a new culture system for assessing replicative lifespan. J Cell Physiol 109: 171–179

    Google Scholar 

  11. Durant S, Duval D, Homo-Delarche F (1986) Factors involved in the control of fibroblast proliferation by glucocorticoids; a review. Endocr Rev 7: 254–269

    Google Scholar 

  12. Dustin ML, Singer KH, Tuck DT, Springer TA (1988) Adhesion of T-lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and mediated by intercellular adhesion molecule (ICAM-1). J Exp Med 267: 1323–1340

    Google Scholar 

  13. Görmar FE, Bernd A, Holzmann H (1990) Wirkung von Hydrocortisonaceponat auf Proliferation, Gesamtprotein- und Kollagen-Synthese menschlicher Hautfibroblasten in vitro. Arzneimittelforschung 40: 192–196

    Google Scholar 

  14. Griffiths CEM, Voorhees JJ, Nickoloff BJ (1989) Characterisation of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumor necrosis factor. J Am Acad Dermatol 20: 617–629

    Google Scholar 

  15. Harvey W, Grahame R, Pnayi GS (1974) Effects of steroid hormones on human fibroblasts in vitro. I. Glucocorticoid action on cell growth and collagen synthesis. Ann Rheum Dis 33: 437–441

    Google Scholar 

  16. Imcke E, Ruszczak Zb, Mayer-da Silva A, Detmar M, Orfanos CE (1991) Cultivation of human dermal microvascular endothelial cells in vitro: Immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res 283: 149–157

    Google Scholar 

  17. Jonson LK, Longenecker JP, Baxter JD, Dallman MF, Widmaier EP, Eberhard NL (1982) Glucocorticoid action: a mechanism involving nuclear and non-nuclear pathways. Br J Dermatol 107 [Suppl]: 6–23

    Google Scholar 

  18. Kondo H, Kasuga H, Noumura T (1985) The heterogeneity of human fibroblasts as determined from the effect of hydrocortisone on cell growth and specific dexamethasone binding. Exp Cell Res 158: 342–348

    Google Scholar 

  19. Kopelovich L (1983) Effect of hydrocortisone on the proliferation of cultured skin fibroblasts from normal individuals and individuals at high risk of colon cancer. Exp Cell Biol 51: 308–314

    Google Scholar 

  20. Lavker RM, Schechter NM, Lazarus GS (1986) Effects of topical corticosteroids on human dermis. Br J Dermatol 115: 101–107

    Google Scholar 

  21. Nickoloff BJ, Lewinsohn D, Butcher E, Krensky AM, Clayberger C (1988) Recombinant gamma interferon increases binding of peripheral blood mononuclear leucocytes and Leu 3+ lymphocyte cell clone to cultured keratinocytes and a malignant cutaneous squamous cell line which is blocked by antibody against the LFA-1 molecule. J Invest Dermatol 90: 17–22

    Google Scholar 

  22. Oikarinen A, Vuorio T, MÄkelÄ J, Vuorio E (1989) 13-cis retinoic acid and dexamethasone modulate the gene expression of epidermal growth factor receptor and fibroblast proteoglycan 40 core protein in human skin fibroblasts. Acta Derm Venereol (Stockh) 69: 466–469

    Google Scholar 

  23. Ponec M, Haas C de, Bachry BN, Polano MK (1977) Effects of glucocorticoids on primary human skin fibroblasts. I. Inhibition of the proliferation of cultured primary human skin and mouse L929 fibroblasts. Arch Dermatol Res 259: 117–123

    Google Scholar 

  24. Renkonen R (1989) Regulation of intercellular adhesion molecule-1 expression of endothelial cells with correlation to lymphocyte-endothelial binding. Scand J Immunol 29: 717–722

    Google Scholar 

  25. Runikis JO, McLean DI, Stewart WD (1978) Growth rate of cultured human fibroblasts increased by glucocorticoids. J Invest Dermatol 70: 348–351

    Google Scholar 

  26. Russell JD, Russell SB, Trupin KM (1978) Differential effects of hydrocortisone on both growth and collagen metabolism of human fibroblasts from normal and keloid tissue. J Cell Physiol 97: 221–230

    Google Scholar 

  27. Ruszczak Zb, Detmar M, Imcke E, Orfanos CE (1990) Effects of rIFN-alpha, rIFN-beta and rIFN-gamma on the morphology, proliferation and cell surface antigen expression of human dermal microvascular endothelial cells in vitro. J Invest Dermatol 95: 693–699

    Google Scholar 

  28. Saarni H, Jalkanen M, Hopsu-Havu VK (1980) Effect of five anti-inflammatory steroids on collagen and glycoaminoglycan synthesis in vitro. Br J Dermatol 103: 167–173

    Google Scholar 

  29. Sawami MK, Lyon MB, Rothlein RR, Norris DA (1989) Study of the effects of corticosteroids and retinoids on the induction of ICAM-1 on cultured human keratinocytes (abstract). Clin Res 38: 695A

    Google Scholar 

  30. Schleimer RP, Freeland HS, Peters SP, Brown KE, Derse CP (1989) An assessment of the effects of glucocorticoids on the degranulation, chemotaxis, binding to vascular endothelium and formation of leukotriene B4 by purified human neutrophils. J Pharmacol Exp Ther 250: 598–605

    Google Scholar 

  31. Schneider EL, Mitsui Y, Au KS, Shorr SS (1977) Tissue-specific differences in cultured human diploid fibroblasts. Exp Cell Res 108: 1–6

    Google Scholar 

  32. Stadler R, Detmar M, Stephanek K, Bangemann C, Orfanos CE (1989) A rapid fluorometric assay for the determination of keratinocyte proliferation in vitro. J Invest Dermatol 93: 532–534

    Google Scholar 

  33. Stoughton RB, Cornell RC (1988) Topical corticosteroids in dermatology. In: Christophers E, Schöpf E, Kligman AM, Stoughton RB (eds) Topical corticosteroid therapy. A novel approach to safer drugs. Raven Press, New York, pp 1–12

    Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, W-1000, Berlin 45, Germany

    U. Hettmannsperger, S. Tenorio, C. E. Orfanos & M. Detmar

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  1. U. Hettmannsperger
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  2. S. Tenorio
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  3. C. E. Orfanos
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  4. M. Detmar
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Hettmannsperger, U., Tenorio, S., Orfanos, C.E. et al. Corticosteroids induce proliferation but do not influence TNF- or IL-1Β-induced ICAM-1 expression of human dermal microvascular endothelial cells in vitro. Arch Dermatol Res 285, 347–351 (1993). https://doi.org/10.1007/BF00371835

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  • DOI: https://doi.org/10.1007/BF00371835

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