Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation
BackgroundEpidemiological 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 alcoho...
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Frontiers Media S.A.
2025-01-01
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| author | Shun Xu Shun Xu Shun Xu Jing Chen Jing Chen Jing Chen Shaoyu Yue Shaoyu Yue Shaoyu Yue Yifan Zhang Yifan Zhang Yifan Zhang Shengyu Zhao Shengyu Zhao Shengyu Zhao Yongtao Hu Yongtao Hu Yongtao Hu Cheng Zhang Cheng Zhang Cheng Zhang Wenrui Guan Wenrui Guan Wenrui Guan Li Zhang Li Zhang Li Zhang Ligang Zhang Ligang Zhang Ligang Zhang Chaozhao Liang Chaozhao Liang Chaozhao Liang |
| author_facet | Shun Xu Shun Xu Shun Xu Jing Chen Jing Chen Jing Chen Shaoyu Yue Shaoyu Yue Shaoyu Yue Yifan Zhang Yifan Zhang Yifan Zhang Shengyu Zhao Shengyu Zhao Shengyu Zhao Yongtao Hu Yongtao Hu Yongtao Hu Cheng Zhang Cheng Zhang Cheng Zhang Wenrui Guan Wenrui Guan Wenrui Guan Li Zhang Li Zhang Li Zhang Ligang Zhang Ligang Zhang Ligang Zhang Chaozhao Liang Chaozhao Liang Chaozhao Liang |
| author_sort | Shun Xu |
| collection | DOAJ |
| description | BackgroundEpidemiological 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.MethodsWe 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.ResultsHE 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.ConclusionOur 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. |
| format | Article |
| id | doaj-art-882af784167240b8afe45bff6b321d92 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-882af784167240b8afe45bff6b321d922025-01-13T13:31:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15124561512456Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiationShun Xu0Shun Xu1Shun Xu2Jing Chen3Jing Chen4Jing Chen5Shaoyu Yue6Shaoyu Yue7Shaoyu Yue8Yifan Zhang9Yifan Zhang10Yifan Zhang11Shengyu Zhao12Shengyu Zhao13Shengyu Zhao14Yongtao Hu15Yongtao Hu16Yongtao Hu17Cheng Zhang18Cheng Zhang19Cheng Zhang20Wenrui Guan21Wenrui Guan22Wenrui Guan23Li Zhang24Li Zhang25Li Zhang26Ligang Zhang27Ligang Zhang28Ligang Zhang29Chaozhao Liang30Chaozhao Liang31Chaozhao Liang32Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Urology, Anhui Medical University, Hefei, Anhui, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, ChinaBackgroundEpidemiological 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.MethodsWe 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.ResultsHE 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512456/fullalcoholCP/CPPSPI3K/AKT/mTOR pathwayTh1 cellmouse model |
| spellingShingle | Shun Xu Shun Xu Shun Xu Jing Chen Jing Chen Jing Chen Shaoyu Yue Shaoyu Yue Shaoyu Yue Yifan Zhang Yifan Zhang Yifan Zhang Shengyu Zhao Shengyu Zhao Shengyu Zhao Yongtao Hu Yongtao Hu Yongtao Hu Cheng Zhang Cheng Zhang Cheng Zhang Wenrui Guan Wenrui Guan Wenrui Guan Li Zhang Li Zhang Li Zhang Ligang Zhang Ligang Zhang Ligang Zhang Chaozhao Liang Chaozhao Liang Chaozhao Liang Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation Frontiers in Immunology alcohol CP/CPPS PI3K/AKT/mTOR pathway Th1 cell mouse model |
| title | Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation |
| title_full | Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation |
| title_fullStr | Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation |
| title_full_unstemmed | Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation |
| title_short | Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation |
| title_sort | alcohol intake exacerbates experimental autoimmune prostatitis through activating pi3k akt mtor pathway mediated th1 differentiation |
| topic | alcohol CP/CPPS PI3K/AKT/mTOR pathway Th1 cell mouse model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512456/full |
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