Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.
Am J Pathol. 2006 September; 169(3): 795–805. doi: 10.2353/ajpath.2006.060079.
Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.
Animals, Apoptosis, Candida albicans, Candidiasis, Combined Modality Therapy, Female, Ficusin, Humans, Hypersensitivity, Delayed, Immune Tolerance, Immunosuppression, Inflammation, Interleukin-10, Lymphoma, T-Cell, Cutaneous, Male, Mice, Mice, Knockout, PUVA Therapy, Platelet Activating Factor, Platelet Membrane Glycoproteins, Psoriasis, Receptors, G-Protein-Coupled, Signal Transduction