title: Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol.
abstract: The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon-gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF- or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production.
authors.affiliation: Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hettmannsperger
authors.forename: M
authors.initials: M
authors.lastname: Detmar
authors.forename: M
authors.initials: M
authors.lastname: Owsianowski
authors.forename: S
authors.initials: S
authors.lastname: Tenorio
authors.forename: H J
authors.initials: HJ
authors.lastname: Kammler
authors.forename: C E
authors.initials: CE
authors.lastname: Orfanos
mesh_terms: D017255:Acitretin / Q000627:therapeutic use; D002117:Calcitriol / Q000494:pharmacology*; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007223:Infant; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000166:cytology; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy; D012867:Skin / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D016572:Cyclosporine; D002117:Calcitriol; D017255:Acitretin; D006854:Hydrocortisone