RELEASE OF INFLAMMATORY MEDIATORS (PGE(2), IL-6) BY FENOFIBRIC ACID-PHOTOSENSITIZED HUMAN KERATINOCYTES AND FIBROBLASTS

Ultraviolet-A radiation has weak effects on the release of inflammator y mediators by skin cells due to the poor overlap between UVA waveleng ths and the absorption spectra of the relevant chromophores of key bio molecules, However, this situation could be very different in the pres ence of a photosensitizing drug. To investigate this issue, we have ir radiated human skin cells (keratinocytes and fibroblasts) in the prese nce of fenofibric acid (the active phototoxic metabolite of fenofibrat e), The results of this research show a dual effect on the production/ release of inflammatory mediators: the synthesis of the proinflammator y cytokine interleukin-6 becomes strongly inhibited at photosensitizer concentrations that clearly stimulate the production of prostaglandin s (PGE,) by skin cells, We have found evidences showing that the de no vo synthesis of cytokines is inhibited in photosensitized cells due to the fact that cellular mRNA is degraded, Interestingly, when the medi um taken from irradiated cultures is added to nonexposed cells, a sign ificant stimulation of cytokine synthesis is observed that can be inhi bited by anti-PGE, antibodies. These observations may be relevant irt vivo, where prostaglandins released by photosensitized skin cells coul d stimulate cytokine synthesis by underlying, nonirradiated cells.