Docosahexaenoic acid mitigates experimental autoimmune prostatitis by inhibiting Th17 cell differentiation via the PPARγ/NF-κB/IL-17A pathway

Abstract Introduction Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urological disorder characterized by urinary symptoms, pelvic pain, and sexual dysfunction. The potential inhibitory effects of docosahexaenoic acid (DHA) in relation to dietary consumption on autoimmune disorders have been acknowledged. Nevertheless, the effect of consuming DHA on CP/CPPS is still uncertain. Methods We established an experimental autoimmune prostatitis (EAP) model, which is frequently employed in CP/CPPS research. Western blotting, RT-qPCR, immunohistochemical staining, hematoxylin and eosin staining, immunofluorescence staining and flow cytometry were used in this study to investigate the effects of dietary docosahexaenoic acid (DHA) intake on EAP and to elucidate the underlying mechanisms involved. During the establishment of EAP, nonobese diabetic (NOD) mice were administered either DHA-enriched water or conventional water. The severity of EAP and the Th17 cell responses were evaluated. Furthermore, we investigated the impact of the PPARγ inhibitor GW9662 and the NF-κB activator on mice with EAP that were administered DHA. Results The findings demonstrated that consumption of DHA reduced the severity of EAP and inhibited the production of Th17 cells. DHA was found to hinder the development of Th17 cells through the PPARγ/NF-κB/IL-17A pathway, as demonstrated by in vitro assays. The administration of GW9662 and NF-κB activator resulted in an increase in Th17 cell production, worsening the symptoms of EAP alleviated by the consumption of DHA. Conclusions The consumption of DHA mitigates EAP by stimulating the PPARγ/NF-κB/IL-17A pathway, thereby influencing the process of Th17 cell differentiation. The results provide a valuable understanding of the molecular pathways that contribute to the beneficial impacts of dietary variables, including DHA, on CP/CPPS.