Phospholipase A ₂ Inhibitors as Potential Treatment of Psoriasis

The phospholipase A 2 (PLA 2 ) enzyme family plays a crucial role in the production of bioactive lipids that are involved in maintaining the epidermal barrier function and regulating inflammation and immune responses in the skin. Therefore, aberrant PLA 2 expression and activity have been implicated in various skin diseases including psoriasis. This review article highlights the potential pathophysiological roles of several secreted and cytosolic PLA 2 s (sPLA 2 and cPLA 2 ) in psoriasis, based on in vitro and in vivo evidence. Based on the available evidence, the PLA 2 enzymes demonstrate diverse roles in psoriatic skin, with several PLA 2 s (e.g., group IIF sPLA 2 and cPLA 2 α) promoting inflammation and aberrant keratinocyte activation and proliferation, while other PLA 2 s (e.g., group IID sPLA 2 and cPLA 2 ε) exhibit anti‐inflammatory or proresolving functions. Thus, targeting specific PLA 2 s for the treatment of psoriasis offers a novel approach beyond conventional immunomodulatory therapies. Although clinical translation of systemic PLA 2 inhibitors has been challenging and unsuccessful thus far, topical PLA 2 inhibitors have demonstrated some potential in the treatment of inflammatory skin diseases. Therefore, continued research on the development of topical PLA 2 inhibitors is needed to provide novel and effective treatment options for psoriasis.