ACTIVATION OF THE EPIDERMAL PLATELET-ACTIVATING-FACTOR RECEPTOR RESULTS IN CYTOKINE AND CYCLOOXYGENASE-2 BIOSYNTHESIS

Recent studies suggest that the lipid mediator platelet-activating fac tor (PAF) is involved in keratinocyte function and skin inflammation, Indeed, PAF is found in association with inflammatory skin diseases, i ntradermal injections of PAF induce inflammation, and keratinocytes ex press functional PAF receptors (PAF-R), One mechanism by which the ker atinocyte PAF-R could contribute to epidermal functions and inflammato ry states would be through the synthesis of inflammatory regulators, s uch as PAF, PGs, and cytokines, The ability of the epidermal PAF-R to induce the synthesis of these immunomodulators was tested using a mode l system created by transduction of the PAF-R-negative human epidermal cell line KB with the PAF-R, Activation of this epidermal PAF-R resul ted in arachidonic acid release, and the biosynthesis of PAF and PGE,, In addition, the KB PAF-R triggered increased levels of mRNA and prot ein for the inducible isozyme of cyclooxygenase (COX-2) as well as IL- 6 and IL-8, both of which have been implicated in skin inflammatory pr ocesses. Studies with the human keratinocyte-derived epidermal cell li ne HaCaT revealed that activation of the endogenous PAF-R led to the i ncreased accumulation of COX-2, IL-6, and IL-8 mRNA similar to that se en with the KB PAF-R model system, Finally, treatment of HaCaT keratin ocytes with IL-8 resulted in PAF biosynthesis, indicating the existenc e of a positive feedback loop between IL-8 and PAF in epidermal cells. These studies suggest involvement of PAF and the PAF-R in the epiderm al cytokine network.