PTGS1 Regulates Macrophage Polarization Through PPARγ Nuclear Translocation to Affect Oxidative Stress Injury in Chronic Prostatitis

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a condition marked by persistent inflammation of the prostate, whose underlying mechanisms remain poorly defined. This study aimed to investigate the role of prostaglandin-endoperoxide synthase 1 (PTGS1) in macrophages and in a mouse model of experimental autoimmune prostatitis (EAP). Using multiple experimental methods, we found that PTGS1 was induced during IL-4-mediated M2 macrophage polarization, whereas PTGS1 silencing further enhanced M2 polarization. Mechanistically, PTGS1 functioned as a feedback regulatory checkpoint by interacting with PPARγ in the cytoplasm and restraining its nuclear translocation; PTGS1 silencing released this constraint, enhanced PPARγ nuclear accumulation, and promoted M2 macrophage polarization. In EAP mice, PTGS1 knockdown alleviated disease progression and reduced oxidative stress injury, accompanied by increased M2 macrophage polarization and reduced iNOS-positive pro-inflammatory macrophage accumulation. Furthermore, PTGS1 silencing diminished the PTGS1-PPARγ interaction, thereby enhancing PPARγ nuclear translocation and strengthening the M2 polarization program. In summary, our findings show that PTGS1 knockdown attenuates F4/80⁺/iNOS⁺ pro-inflammatory macrophage accumulation, mitigates prostatic inflammation and oxidative stress, and offers a potential immunomodulatory strategy for CP/CPPS.