Scholarlink

<p>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, <i>Parp1</i><sup>−/−</sup> 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 <i>Parp1</i><sup>−/−</sup> prostatitic mice decreased. <i>In vitro</i> experiments revealed that M1(CD206<sup>−</sup>CD86<sup>+)</sup> macrophage in LPS-induced macrophage of <i>Parp1</i><sup>−/−</sup> 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 <i>via</i> the NF-κB pathway, suggesting PARP1 could be a potential therapeutic target for macrophage-based treatments in prostatitis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月4日

查看全文
  • Lu Jin,
  • Jiaxing Chen,
  • Jianhui Fu,
  • Jingyi Lou,
  • Yingxue Guo,
  • Xia Liu,
  • Xiaojuan Xu,
  • Huiying Fu,
  • Qiyang Shou

摘要

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.