Involvement of P38 MAP kinase in the augmentation of UVB-mediated apoptosis via the epidermal platelet-activating factor receptor

Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects, which are mediated by the PAF receptor (PAF-R). Our previous studies have demonstrated that ultraviolet B radiation (UVB) is a potent stimulus for PAF production, and that the presence of the PAF-R on epithelial cells results in an augmentation of UVB-induced apoptosis. Inasmuch as PAF-R activation results in numerous signal transduction pathways, the present study was designed to characterize the signal transduction pathway responsible for PAF-R-mediated enhanced UVB-induced cytotoxicity. Using a model system of PAF-R-negative and -positive epithelioid KB cells, we demonstrate that inhibitors of p38 MAP kinase block the augmentation of UVB-mediated apoptosis seen in PAF-R-positive KB cells. In contrast, pharmacological and/or molecular inhibition of other pathways linked to PAF-R activation including ERK MAP kinase and NF kappa B do not affect PAF-R-mediated cytotoxicity. This study demonstrates the important role that p38 MAP kinase plays in PAF-R-mediated augmentation of UVB cytotoxicity.