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二十二碳六烯酸通过PPARγ/NF-κB/IL-17A途径抑制Th17细胞分化来减轻实验性自身免疫性前列腺炎。

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

作者信息

Wu Weikang, Yue Shaoyu, Wang Xu, Li WeiYi, Xu Lingfan, Guan Yu, Liang Chao-Zhao

机构信息

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, PR China.

Institute of Urology, Anhui Medical University, Hefei, PR China.

出版信息

Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxaf055.

DOI:10.1093/cei/uxaf055
PMID:40887935
Abstract

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. Therefore, we established an experimental autoimmune prostatitis (EAP) model, which is frequently employed in CP/CPPS research. This study aimed to investigate the effects of dietary docosahexaenoic acid (DHA) intake on EAP and to elucidate the underlying mechanisms involved. During the establishment of EAP, non-obese 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 PMA on mice with EAP that were administered DHA. 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 PMA resulted in an increase in Th17 cell production, worsening the symptoms of EAP alleviated by the consumption of DHA. The present study revealed that 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.

摘要

慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)是一种常见的泌尿系统疾病,其特征为尿路症状、盆腔疼痛和性功能障碍。二十二碳六烯酸(DHA)在饮食摄入方面对自身免疫性疾病的潜在抑制作用已得到认可。然而,摄入DHA对CP/CPPS的影响仍不确定。因此,我们建立了一种常用于CP/CPPS研究的实验性自身免疫性前列腺炎(EAP)模型。本研究旨在探讨饮食中摄入二十二碳六烯酸(DHA)对EAP的影响,并阐明其中涉及的潜在机制。在EAP模型建立过程中,给非肥胖糖尿病(NOD)小鼠饮用富含DHA的水或普通水。评估EAP的严重程度和Th17细胞反应。此外,我们研究了PPARγ抑制剂GW9662和NF-κB激活剂PMA对摄入DHA的EAP小鼠的影响。研究结果表明,摄入DHA可降低EAP的严重程度并抑制Th17细胞的产生。体外实验表明,DHA通过PPARγ/NF-κB/IL-17A途径阻碍Th17细胞的发育。给予GW9662和PMA导致Th17细胞产生增加,使摄入DHA缓解的EAP症状恶化。本研究表明,摄入DHA通过刺激PPARγ/NF-κB/IL-17A途径减轻EAP,从而影响Th17细胞分化过程。这些结果为理解饮食变量(包括DHA)对CP/CPPS产生有益影响的分子途径提供了有价值的见解。

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