4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway

作者全名："Zhao, Xiaohu; Feng, Rui; Chen, Juan; Jiang, Qing; Hua, Xiaoliang; Liang, Chaozhao"

作者地址："[Zhao, Xiaohu; Feng, Rui; Liang, Chaozhao] Anhui Med Univ, Affiliated Hosp 1, Dept Urol, Hefei, Peoples R China; [Zhao, Xiaohu; Feng, Rui; Jiang, Qing; Hua, Xiaoliang] Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, Chongqing, Peoples R China; [Chen, Juan] Chongqing Med Univ, Coll Lab Med, Minist Educ, Key Lab Lab Med Diagnost, Chongqing, Peoples R China; [Liang, Chaozhao] Anhui Med Univ, Affiliated Hosp 1, Dept Urol, 218 Jixi Rd, Hefei 230022, Peoples R China; [Hua, Xiaoliang] Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Liang, CZ (通讯作者)，Anhui Med Univ, Affiliated Hosp 1, Dept Urol, 218 Jixi Rd, Hefei 230022, Peoples R China.; Hua, XL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：PROSTATE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001118553700001

JCR分区：Q2

影响因子：2.6

年份：2024

卷号：84

期号：4

开始页：329

结束页：341

文献类型：Article; Early Access

关键词：4-Octyl itaconate; chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS); inflammation; pyroptosis

摘要："BackgroundChronic prostatitis demonstrates a prevalence rate of nearly 5%-10% among young and middle-aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti-inflammatory properties of itaconic acid (IA) and its derivative, 4-Octyl itaconate (4-OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti-inflammatory effects in chronic prostatitis requires extensive research and validation.MethodsHuman prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune-responsive gene 1 (IRG-1) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4-OI, while the control group received injections of saline. Western blot (WB), H&E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme-linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups.ResultsIHC analysis of human prostate tissue depicts that IRG-1 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4-OI increased Nrf2/HO-1 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1 h before intraperitoneal injection of 50 mg/kg 4-OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL-1 beta, IL-6, and TNF-alpha), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti-inflammatory effects of 4-OI in EAP.ConclusionsThe present study indicates that 4-OI can alleviates EAP by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway, which may facilitate a novel approach toward prostatitis treatment."

基金机构：National Natural Science Foundation of China; Natural Science Foundation of Chongqing Science and Technology [CSTB2023NSCQ-BHX0040]; China Postdoctoral Science Foundation [2023M730445]; [82300873]

基金资助正文："This study was funded by the National Natural Science Foundation of China (82170787) to Liang chaozhao and the National Natural Science Foundation of China (82300873), Natural Science Foundation of Chongqing Science and Technology (CSTB2023NSCQ-BHX0040), China Postdoctoral Science Foundation (2023M730445) to Xiaoliang Hua."