Evidence for involvement of the epidermal platelet-activating factor receptor in ultraviolet-B-radiation-induced interleukin-8 production

Ultraviolet B radiation has been shown to generate cutaneous inflammation i n part through inducing oxidative stress and cytokine production in human k eratinocytes. Amongst the proinflammatory cytokines synthesized in response to ultraviolet B radiation is the potent chemoattractant interleukin-8. Th ough the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and keratinocytes express PAF receptors linke d to cytokine biosynthesis, it is not known whether PAF is involved in ultr aviolet-B-induced epidermal cell cytokine production. These studies examine d the role of the PAF system in ultraviolet-B-induced epidermal cell interl eukin-8 biosynthesis using a novel model system created by retroviral-media ted transduction of the PAF-receptor-negative human epidermal cell line KB with the human PAF receptor. Treatment of PAF-receptor-expressing KB cells with the metabolically stable PAF receptor agonist carbamoyl-PAF resulted i n increased interleukin-8 mRNA and protein, indicating that activation of t he epidermal PAF receptor was linked to interleukin-8 production. Ultraviol et B irradiation of PAF-receptor-expressing KB cells resulted in significan t increases in both interleukin-8 mRNA and protein in comparison to ultravi olet-B-treated control KB cells. Pretreatment with PAF receptor antagonists inhibited both carbamoyl-PAF-induced and ultraviolet-B-induced interleukin -8 production in the PAF-receptor-positive cells, but not in control KB cel ls. Similarly, treatment of the PAF-receptor-expressing primary cultures of human keratinocytes or the human epidermal cell line A-431 with carbamoyl- PAF or ultraviolet B radiation resulted in interleukin-8 production that wa s partially inhibited by PAF receptor antagonists. These studies suggest th at the epidermal PAF receptor may be a pharmacologic target for ultraviolet B radiation in skin and thus may act to augment ultraviolet-B-mediated pro duction of cytokines such as interleukin-8.