Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1512456
This article is part of the Research Topic Immunoregulation in Urological Disorders: Novel Targets and Therapies View all 3 articles

Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation

Provisionally accepted
Ligang Zhang Ligang Zhang *Shun Xu Shun Xu Jing Chen Jing Chen Shaoyu Yue Shaoyu Yue Yifan Zhang Yifan Zhang Shengyu Zhao Shengyu Zhao Yongtao Hu Yongtao Hu Cheng Zhang Cheng Zhang Wenrui Guan Wenrui Guan Li Zhang Li Zhang Chaozhao Liang Chaozhao Liang
  • Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

The final, formatted version of the article will be published soon.

    Backgroud: Epidemiological investigations have revealed a significant association between alcohol consumption and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Nevertheless, the potential mechanisms are still inadequately revealed. This research aimed to investigate the impact of alcohol on CP/CPPS using an animal model and to elucidate the underlying mechanisms.We first established the widely used animal model for CP/CPPS, experimental autoimmune prostatitis (EAP). During the induction of EAP, mice were fed with alcohol or control diet. The HE staining, ELISA, and behavioral experiments were employed to assess the severity of inflammation in EAP mice and EAP-alcohol mice. Patients with a history of chronic alcohol consumption were also included to evaluate the effects of chronic alcohol consumption on CP/CPPS. Subsequently, proteomic analysis, flow cytometry, immunofluorescence, Western blotting, and immunohistochemistry were utilized to investigate the underlying mechanism involved both in vivo and in vitro.Results: HE staining, ELISA, and behavioral experiments showed that alcohol exacerbated the severity of EAP in mice and patients. Proteomic and KEGG pathway analyses showed that abnormal Th1 differentiation and PI3K/AKT/mTOR pathway were significantly enriched. Subsequent mechanistic research showed that alcohol significantly activated PI3K/AKT/mTOR pathway and increased the Th1 cell differentiation both in vivo and in vitro. In contrast, PI3K inhibitor LY294002 and shRNA-PI3K plasmid inhibited PI3K/AKT/mTOR pathway activation, reduced Th1 cell differentiation, and alleviated EAP inflammation severity, respectively.Our study is the first to demonstrate that alcohol intake promotes Th1 cell differentiation and exacerbates EAP by activating the PI3K/AKT/mTOR pathway. Additionally, the role of LY294002 in inhibiting PI3K/AKT/mTOR pathway to relieve EAP suggests that it can serve as a promising therapeutic target for CP/CPPS.

    Keywords: alcohol, CP/CPPS, PI3K/Akt/mTOR pathway, Th1 cell, mouse model

    Received: 16 Oct 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Zhang, Xu, Chen, Yue, Zhang, Zhao, Hu, Zhang, Guan, Zhang and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ligang Zhang, Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.