DOSE-DEPENDENT INDUCTION OF IL-12 BUT NOT IL-10 FROM HUMAN KERATINOCYTES AFTER EXPOSURE TO ULTRAVIOLET-LIGHT-A

Ultraviolet light A (UVA) is shown to play an augmentative or synergis tic role with UVB in pathophysiological conditions induced by solar ra diation. Thus, UVA would contribute significantly to the development o f skin malignancies. It remains unclear, however, how UVA contributes to solar radiation-induced immune suppression. Keratinocytes (KC) prod uce cytokines which are a significant mediator of inflammatory and imm unologic reactions in skin exposed to solar radiation and are a potent mediator in the induction of immune suppression. To examine if UVA al ters the expression and production of cytokines from KC, normal human keratinocytes (HuSK) were cultured and exposed to UVA at doses ranging between 2.5 and 20 kJ/m(2). Constitutive expression of the p35 subuni t of interleukin (IL)-12 was detected by reverse transcription-polymer ase chain reaction (RT-PCR) and the p40 subunit was induced by UVA irr adiation dose dependently. IL-12 protein was also detected in the supe rnatants from UVA-irradiated HuSK by enzyme-linked imuunosorbent assay (ELISA) and confirmed by a bioassay. On the other hand, the same dose s of UVA did not induce IL-10 mRNA or IL-10 protein which has been sho wn to be one of the cytokines responsible for the induction of UVB-ind uced immunosuppression. Considering that IL-12 promotes activation of Th1 cells and prevents the activation of Th2 cells and that administra tion of IL-12 has been shown to block the induction of immune suppress ion in UV-irradiated animals, our results suggest that UVA modulates s kin immune function distinctively from UVB by affecting the balance be tween IL-10 and IL-12 produced from KC. (C) 1998 Wiley-Liss, Inc.