Vitamin E alleviates experimental autoimmune prostatitis by inhibiting the EGFR/MAPK pathway to reduce M1 macrophage polarization

  • Int Immunopharmacol. 2026 Jun 1:178:116568. doi: 10.1016/j.intimp.2026.116568.
Yifan Zhang  1 ,  Shun Xu  1 ,  Cheng Zhang  1 ,  Shengyu Zhao  1 ,  Xiaoran Dai  2 ,  Han Yang  1 ,  Jialong Zhang  1 ,  Zhihui Zou  3 ,  Chaozhao Liang  4 ,  Ligang Zhang  5
Affiliations
  • 1. Department of Urology, the First AffiliatedHospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China; Institute of Urology, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, China.
  • 2. Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University,Hefei, China.
  • 3. Department of Urology, the First AffiliatedHospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China; Institute of Urology, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, China. Electronic address: [email protected].
  • 4. Department of Urology, the First AffiliatedHospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China; Institute of Urology, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, China. Electronic address: [email protected].
  • 5. Department of Urology, the First AffiliatedHospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China; Institute of Urology, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, China. Electronic address: [email protected].
PMID: 41915990 DOI: 10.1016/j.intimp.2026.116568
Abstract

A major urological condition that manifests in the form of urinary abnormalities, pelvic region pain, and sexual problems is known as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The underlying pathogenesis of this disorder remains poorly understood.. The effects of vitamin E (VitE) on mitigating CP/CPPS were investigated here. In individuals with CP/CPPS, serum pro-inflammatory factors were found to be significantly increased. A mouse model of experimental autoimmune prostatitis (EAP) and RAW264.7 mouse macrophages were used to evaluate the effects of VitE. The results showed that VitE administration significantly and dose-dependently ameliorated prostatic inflammatory infiltration and pain in EAP mice, and decreased the serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Similar reductions were observed in the culture supernatants of RAW264.7 cells. Mechanistic studies revealed that VitE potently suppressed macrophage M1 polarization by downregulating epidermal growth factor receptor (EGFR) and decreasing phosphorylation of its downstream mitogen-activated protein kinase (MAPK) pathway components. Treatment with the EGFR agonist NSC228155 or overexpression of EGFR in cells counteracted the effects of VitE, reversing its anti-inflammatory effects and promoting M1 polarization. Molecular docking and surface plasmon resonance (SPR) analyses confirmed direct binding between VitE and EGFR. In summary, this study reveals that VitE alleviates CP/CPPS at least in part by inhibiting the EGFR/MAPK axis, thereby reducing M1 macrophage polarization. These findings provide a theoretical foundation for the potential use of VitE in CP/CPPS treatment.

Keywords
EGFR/MAPK; Macrophage; Prostatitis; Vitamin E.
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