Prdx5 regulates macrophage polarization by modulating the TLR4/NF-κB pathway to promote apoptosis in chronic prostatitis

Abstract

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urological disorder characterized by urinary symptoms, pelvic pain, and sexual dysfunction. Despite its high prevalence, the pathogenesis of CP/CPPS remains poorly understood. Our study revealed that peroxiredoxin 5 (Prdx5) was upregulated in M1 macrophages and in mice with experimental autoimmune prostatitis (EAP), with its expression in macrophages being regulated in a reactive oxygen species (ROS)-dependent manner. Using western blotting, RT-qPCR, immunohistochemical staining, hematoxylin and eosin staining, immunofluorescence staining, flow cytometry, and cell co-culturing, it was demonstrated that the silencing of Prdx5 suppressed the polarization of macrophages towards the M1 phenotype. This inhibition reduced apoptosis in prostate epithelial cells and mitigated the progression of EAP. Furthermore, Prdx5 mediated its effects in macrophages and EAP via the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway. Our findings suggest that Prdx5 promoted the occurrence and development of CP/CPPS due to its promotion of M1 polarization and apoptosis of prostate epithelial cells in an ROS-dependent manner via the TLR4/NF-κB axis, indicating its potential as a therapeutic target to treat CP/CPPS.