Corticosteroids induce proliferation but do not influence TNF- or IL-1 beta-induced ICAM-1 expression of human dermal microvascular endothelial cells in vitro.
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-1 beta (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-1 beta 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.
Hettmannsperger
U
U
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, Germany.
Tenorio
S
S
Orfanos
C E
CE
Detmar
M
M
D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D001624:Betamethasone Valerate / Q000009:adverse effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002990:Clobetasol / Q000009:adverse effects / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D013684:Telangiectasis / Q000139:chemically induced / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D001624:Betamethasone Valerate; D002990:Clobetasol; D006854:Hydrocortisone