INTERLEUKIN-1 RECEPTORS TYPE-I AND TYPE-II ARE DIFFERENTIALLY REGULATED IN HUMAN KERATINOCYTES BY ULTRAVIOLET-B RADIATION

Since regulation of keratinocyte IL-1 receptor expression is likely to have a major impact on the biologic effects of IL-1 on epidermal cell s, we examined expression, regulation, and function of IL-1R in cultur ed human keratinocytes, By reverse transcriptase polymerase chain reac tion, human keratinocytes were shown to express IL-1 receptor type I ( IL-1RI) and IL-1 receptor type II (IL-1RII). Human keratinocyte IL-1RI mRNA expression was dependent on the differentiation state of the cel l and was regulated by ultraviolet B (UVB) radiation, which initially decreased but later increased IL-1RI expression. This UVB-induced biph asic modulation of IL-1RI expression was mediated by an autocrine mech anism involving endogenously produced IL-1 alpha and IL-1RI. Increased expression of IL-1RI in UVB-irradiated or IL-1 alpha-stimulated kerat inocytes was functionally important, because it endowed these cells wi th the capacity to upregulate expression of the intercellular adhesion molecule (ICAM)-1 upon IL-1 alpha stimulation, Keratinocyte IL-1RII e xpression was regulated by UVB irradiation in an inverse manner, Signi ficant and rapid upregulation of IL-1RII was observed within 1 h after UVB irradiation and gradually decreased to background levels within 2 4 h. Inverse regulation of IL-1RII versus IL-1RI was associated with o pposite functions, because blocking of IL-1RII enhanced IL-1 alpha eff ects on induction of ICAM-1 expression, These studies demonstrate that IL-1 responsiveness of UVB-irradiated keratinocytes critically depend s on regulation of IL-1RI expression and that IL-1RII serves as a ''de coy'' receptor for IL-1, limiting rather than promoting IL-1-mediated effects.