2. Academic Validation
  3. MIF aggravates experimental autoimmune prostatitis through activation of the NLRP3 inflammasome via the PI3K/AKT pathway

MIF aggravates experimental autoimmune prostatitis through activation of the NLRP3 inflammasome via the PI3K/AKT pathway

  • Int Immunopharmacol. 2024 Nov 15:141:112891. doi: 10.1016/j.intimp.2024.112891.
Fei Zhang 1,  Tong Meng 1,  Rui Feng 2,  Chen Jin 1,  Song Zhang 1,  Jialin Meng 1,  Meng Zhang 3,  Chaozhao Liang 4
Affiliations

Affiliations

  • 1 Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China; Institute of Urology, Anhui Medical University, Hefei 230022, PR China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, PR China.
  • 2 Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China; Institute of Urology, Anhui Medical University, Hefei 230022, PR China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, PR China; Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
  • 3 Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China; Institute of Urology, Anhui Medical University, Hefei 230022, PR China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, PR China. Electronic address: zhangmeng1930@126.com.
  • 4 Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China; Institute of Urology, Anhui Medical University, Hefei 230022, PR China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, PR China. Electronic address: liang_chaozhao@ahmu.edu.cn.
PMID: 39153310 DOI: 10.1016/j.intimp.2024.112891
Abstract

In our investigation, we investigated the role of macrophage migration inhibitory factor (MIF), a key cytokine, in chronic nonbacterial prostatitis (CNP), an underexplored pathology. Elevated MIF expression was observed in the serum of individuals with chronic prostatitis-like symptoms (CP-LS) as well as in serum and tissue samples from experimental autoimmune prostatitis (EAP) mouse model. Treatment with ISO-1, a specific MIF antagonist, effectively mitigated prostatic inflammation and macrophage infiltration, thereby emphasizing the critical role of MIF in orchestrating immune responses within the prostate microenvironment. Further analyses revealed that MIF stimulates the PI3K/Akt and NLRP3 inflammasome pathways, which are integral to inflammation and cellular immunity. Pharmacological inhibition of the PI3K/Akt pathway by LY294002 substantially reduced prostatic inflammation and macrophage infiltration, potentially by inhibiting NLRP3 inflammasome activation. These findings collectively suggest that MIF is a potential diagnostic marker for CNP and suggest that targeting MIF or its downstream signalling pathways, PI3K/Akt and NLRP3, might represent a novel therapeutic strategy for this condition.

Keywords

Chronic nonbacterial prostatitis; ISO-1; Macrophage migration inhibitory factor; NLRP3 inflammasome; PI3K/AKT.

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