INTERLEUKIN-10 PRODUCTION BY CULTURED HUMAN KERATINOCYTES - REGULATION BY ULTRAVIOLET-B AND ULTRAVIOLET A1 RADIATION

Keratinocytes are the primary cellular target for ultraviolet radiatio n in human skin, and ultraviolet radiation-induced therapeutical effec ts may thus be mediated by keratinocyte-derived, antiinflammatory medi ators, Interleukin-10 is capable of exerting antiinflammatory effects by virtue of its capacity to suppress the production of interferon-gam ma, The present study therefore assessed the ability of cultured human keratinocytes to produce interleukin-10 following ultraviolet irradia tion, Exposure of long-term cultured normal human keratinocytes to ult raviolet B (280-320 nm) or to ultraviolet A1 (340-400 mn) radiation ca used a time- and dose-dependent induction of interleukin-10 mRNA expre ssion and interleukin-10 protein secretion, with ultraviolet Al radiat ion being the strongest stimulus, Ultraviolet radiation-induced interl eukin-10 production by normal human keratinocytes was enhanced by a fa ctor of two, when cells were cultured in high- rather than low-calcium medium, Neither addition of the ultraviolet radiation-inducible cytok ines tumor necrosis factor-alpha or interleukin-1 alpha to unirradiate d keratinocytes nor presence of their respective neutralizing antibodi es in cultures of irradiated keratinocytes induced or inhibited interl eukin-10 synthesis, Modulation of eicosanoid production by addition of prostaglandin E(2) to keratinocyte cultures or disturbance of cycloox ygenase activity by indomethacin did not affect interleukin-10 product ion in resting or irradiated cells, These studies demonstrate that cul tured human keratinocytes are capable of producing interleukin-10. Hum an keratinocyte interleukin-10 production is dependent on the differen tiation state of the cell and induced by ultraviolet B and, in particu lar, ultraviolet Ai radiation exposure, This novel property of ultravi olet radiation may account at least in part for the efficacy of photot herapy in inflammatory skin diseases.