Resolvin D5n-3 DPA protects against lung injury by modulating the NLRP3 inflammasome and immune pathways

Oxylipins, a class of oxidized fatty acid derivatives, are emerging as critical mediators in the regulation and resolution of inflammation. Among them, Resolvin D5n-3 DPA (RvD5n-3 DPA) is a potent specialized pro-resolving lipid, yet its role in pulmonary inflammation remains poorly understood. Here, we demonstrate that RvD5n-3 DPA exerts robust immunomodulatory and tissue-protective effects in both human lung epithelial cells and murine models of poly(I:C)-induced viral-like lung injury. Treatment with RvD5n-3 DPA significantly attenuated inflammation, oxidative stress, mucus hypersecretion, and fibrosis. Notably, RvD5n-3 DPA modulated NLRP3-inflammasome-related signaling in association with these protective effects. Given the central role of NLRP3 in the pathogenesis of various inflammatory lung diseases, our findings highlight RvD5n-3 DPA as a promising therapeutic candidate for both acute and chronic pulmonary disorders. Furthermore, this study underscores the broader therapeutic potential of oxylipins as nutraceutical interventions to promote respiratory health and prevent inflammation-driven lung injury.