title: Ultraviolet B light stimulates interleukin-20 expression by human epithelial keratinocytes.
abstract: The proinflammatory cytokine interleukin-20 (IL-20) may exert the majority of its activity in the skin. We examined the effect of various treatments including several forms of phototherapy on IL-20 expression using cultured normal human epithelial keratinocytes (NHEK). Broadband UVB light, recombinant (r) IL-1 and rIL-8 increased, while hydrocortisone reduced, NHEK supernatant IL-20 levels. Elevation of NHEK IL-20 mRNA and maximal supernatant IL-20 levels occurred with a UVB light dose (40 mJ cm(-2)) that reduced cell viability by approximately 50%. While this UVB light dose also elevated supernatant IL-1 alpha and IL-8 levels, antibody neutralization studies indicated that neither of these cytokines was directly responsible for this increase in IL-20 expression. However, the elevation in IL-20 levels was fully inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB-203580, suggesting involvement of this stress signaling pathway in this UVB light response. Photodynamic therapy (PDT) with the photosensitizer lemuteporfin, UVA light, cisplatin, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) or recombinant interferon-gamma (rIFN-gamma) either had little effect or decreased NHEK supernatant IL-20 levels. Reduced IL-20 levels paralleled the cytotoxic actions of PDT, UVA light or cisplatin and the antiproliferative effect of rIFN-gamma. Neither rIL-20 supplementation nor anti-IL-20 antibody treatments affected cell viability indicating that soluble IL-20 did not affect the short-term survival of UVB light-irradiated NHEK. Stimulation of IL-20 expression in keratinocytes by UVB light suggests that this cytokine might participate in skin responses to this ever-present environmental factor and potentially has a role in UV light-associated dermatoses.
authors.affiliation: Scientific Affairs: Dermatology, QLT, Inc., Vancouver, British Columbia, Canada. dhunt@qltinc.com
authors.forename: David W C
authors.initials: DW
authors.lastname: Hunt
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Boivin
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Fairley
authors.forename: Miroslava M
authors.initials: MM
authors.lastname: Jovanovic
authors.forename: Diane E
authors.initials: DE
authors.lastname: King
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Salmon
authors.forename: Oliver B
authors.initials: OB
authors.lastname: Utting
mesh_terms: D002945:Cisplatin / Q000494:pharmacology; D017931:DNA Primers; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005026:Ethylene Glycols / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D011166:Porphyrins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers; D005026:Ethylene Glycols; D007378:Interleukins; D011166:Porphyrins; C510896:lemuteporfin; D002945:Cisplatin; C422042:interleukin 20