Augmentation of ultraviolet B radiation-induced tumor necrosis factor production by the epidermal platelet-activating factor receptor

Ultraviolet B radiation (UVB) has been shown to damage human keratinocytes in part by inducing oxidative stress and cytokine production. Indeed, UVB-i nduced production of the pro-inflammatory and cytotoxic cytokine tumor necr osis factor alpha (TNF-alpha) has been implicated in the epidermal damage s een in response to acute solar radiation, Though the lipid mediator platele t-activating factor (PAF) is synthesized in response to oxidative stress, a nd keratinocytes express PAF receptors linked to cytokine biosynthesis, it is not known whether PAF is involved in UVB-induced epidermal cell cytokine production. These studies examined the role of the PAF system in UVB-induc ed epidermal cell TNF-alpha biosynthesis using a novel model system created by retroviral-mediated transduction of the PAF receptor-negative human epi dermal cell line KB with the human PAF receptor (PAF-R). Treatment of PAF-R -expressing RE cells with the metabolically stable PAF-R agonist carbamoyl- PAF resulted in increased TNF-alpha mRNA and protein, indicating that activ ation of the epidermal PAF-R was linked to TNF-alpha production. UVB irradi ation of PAP-R-expressing KB cells resulted in significant increases in bot h TNF-alpha mRNA and protein in comparison to UVB-treated control KB cells. However, UVB treatment up-regulated cyclooxygenase-2 mRNA levels to the sa me extent in both PAF-R-expressing and control KB cells. Pretreatment with the antioxidant vitamin E or the PAF-R antagonists WEB 2086 and A-85783 inh ibited UVB-induced TNF-alpha production in the PAF-R-positive but not contr ol KB cells. These studies suggest that the epidermal PAF-R may be a pharma cological target for UVB in skin.