PARP1 Exacerbates Prostatitis by Promoting M1 Macrophages Polarization through NF-κB Pathway.

Abstract

PARP1 is recognized for its role as a DNA damage sensor and its involvement in inflammatory diseases, but its impact on prostatitis remains unclear. We aimed to elucidate how PARP1 affects prostatitis progression. Our results showed that in 1% carrageenan-induced prostatitis mouse model, Parp1^-/- prostatitic mice showed less pathological damage, decreased prostate weight, and lower inflammatory indices, decreased macrophage and neutrophil infiltration, down-regulated the expression of pro-inflammatory cytokines (IL-6, IL-12p70, CCL2, TNF) and up-regulated anti-inflammatory cytokine IL-10 in prostate tissue. The expression of NF-κB, TNF, and IL-6 mRNA in the prostate tissue of Parp1^-/- prostatitic mice decreased. In vitro experiments revealed that M1(CD206^-CD86⁺⁾ macrophage in LPS-induced macrophage of Parp1^-/- mice decreased, as did iNOS, TNF, IL-6 and NF-κB mRNA expression. Mechanically, treatment with the PARP1 inhibitor (AG14361) led to a significant reduction in NF-κB mRNA and Phospho-NF-κB P65 protein expression in macrophages. Following intervention with NF-κB inhibitors (Bay 11-7082), both IL-6 protein and mRNA levels were markedly diminished, meanwhile the secretion of IL-6, IL-10, IL-12p70, CCL2, IFN-γ, and TNF exhibited a pronounced dose-dependent decrease. Collectively, these findings indicated that PARP1 exacerbates carrageenan-induced prostatitis by promoting M1 macrophages polarization via the NF-κB pathway, suggesting PARP1 could be a potential therapeutic target for macrophage-based treatments in prostatitis.