title: Interleukin-10 production by cultured human keratinocytes: regulation by ultraviolet B and ultraviolet A1 radiation.
abstract: Keratinocytes are the primary cellular target for ultraviolet radiation in human skin, and ultraviolet radiation-induced therapeutical effects may thus be mediated by keratinocyte-derived, antiinflammatory mediators. Interleukin-10 is capable of exerting antiinflammatory effects by virtue of its capacity to suppress the production of interferon-gamma. The present study therefore assessed the ability of cultured human keratinocytes to produce interleukin-10 following ultraviolet irradiation. Exposure of long-term cultured normal human keratinocytes to ultraviolet B (280-320 nm) or to ultraviolet A1 (340-400 nm) radiation caused a time- and dose-dependent induction of interleukin-10 mRNA expression and interleukin-10 protein secretion, with ultraviolet A1 radiation being the strongest stimulus. Ultraviolet radiation-induced interleukin-10 production by normal human keratinocytes was enhanced by a factor of two, when cells were cultured in high- rather than low-calcium medium. Neither addition of the ultraviolet radiation-inducible cytokines tumor necrosis factor-alpha or interleukin-1 alpha to unirradiated keratinocytes nor presence of their respective neutralizing antibodies in cultures of irradiated keratinocytes induced or inhibited interleukin-10 synthesis. Modulation of eicosanoid production by addition of prostaglandin E2 to keratinocyte cultures or disturbance of cyclooxygenase activity by indomethacin did not affect interleukin-10 production in resting or irradiated cells. These studies demonstrate that cultured human keratinocytes are capable of producing interleukin-10. Human keratinocyte interleukin-10 production is dependent on the differentiation state of the cell and induced by ultraviolet B and, in particular, ultraviolet A1 radiation exposure. This novel property of ultraviolet radiation may account at least in part for the efficacy of phototherapy in inflammatory skin diseases.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Grewe
authors.forename: K
authors.initials: K
authors.lastname: Gyufko
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology / Q000528:radiation effects; D015232:Dinoprostone / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology / Q000528:radiation effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D015230:Prostaglandin D2 / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014466:Ultraviolet Rays
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D012333:RNA, Messenger; D016753:Interleukin-10; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin