Scholarlink

<p>Damage-associated molecular patterns (DAMPs) are a cause of Crohn’s disease (CD). Peroxiredoxin 1 (Prdx1), a newly identified DAMP, plays a critical role in organ injury with its potent proinflammatory properties. However, its specific role in CD remains unclear. Here, we identify serum Prdx1 as a DAMP involved in CD. Serum Prdx1 levels were significantly increased and positively correlated with the severity of intestinal inflammation in both CD patients and mice with experimental colitis. Genetic knockout of <i>Prdx1</i> or administration of a Prdx1-neutralizing antibody attenuated colitis in mice, as evidenced by restoration of the colonic epithelium, improved disease activity, and reduced colonic inflammation. These protective effects were impaired by introduction of recombinant Prdx1 (rPrdx1). Mechanistically, Prdx1 exacerbated intestinal inflammation by promoting macrophage infiltration and subsequent cytokine production. Depletion of macrophages abolished the rPrdx1-mediated exacerbation of colitis. Further, rPrdx1 was internalized by macrophages, leading to lysosomal disruption and subsequent activation of the NLRP3 inflammasome. Pharmacological inhibition of NLRP3 effectively abrogated rPrdx1-induced exacerbation of colitis. In conclusion, serum Prdx1 promotes intestinal inflammation in CD at least in part by activating the NLRP3 inflammasome through lysosomal disruption in macrophages. These findings highlight the pathogenic role of Prdx1 in CD and reveal therapeutic potential of managing CD via neutralization of circulating Prdx1.</p><p></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

Peroxiredoxin 1 promotes intestinal inflammation by activating the NLRP3 inflammasome in macrophages through lysosomal disruption in Crohn’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月26日

查看全文
  • Shenglan Li,
  • Qiuping Xia,
  • Ying He,
  • Wei Wu,
  • Damu Tang,
  • Zhenghao Deng,
  • Zhijun Zeng,
  • Sha Tu,
  • Bo Chen,
  • Lei Gu,
  • Xinyi Yang,
  • Yu Peng,
  • Huixiang Yang,
  • Zhangzhe Peng

摘要

Damage-associated molecular patterns (DAMPs) are a cause of Crohn’s disease (CD). Peroxiredoxin 1 (Prdx1), a newly identified DAMP, plays a critical role in organ injury with its potent proinflammatory properties. However, its specific role in CD remains unclear. Here, we identify serum Prdx1 as a DAMP involved in CD. Serum Prdx1 levels were significantly increased and positively correlated with the severity of intestinal inflammation in both CD patients and mice with experimental colitis. Genetic knockout of Prdx1 or administration of a Prdx1-neutralizing antibody attenuated colitis in mice, as evidenced by restoration of the colonic epithelium, improved disease activity, and reduced colonic inflammation. These protective effects were impaired by introduction of recombinant Prdx1 (rPrdx1). Mechanistically, Prdx1 exacerbated intestinal inflammation by promoting macrophage infiltration and subsequent cytokine production. Depletion of macrophages abolished the rPrdx1-mediated exacerbation of colitis. Further, rPrdx1 was internalized by macrophages, leading to lysosomal disruption and subsequent activation of the NLRP3 inflammasome. Pharmacological inhibition of NLRP3 effectively abrogated rPrdx1-induced exacerbation of colitis. In conclusion, serum Prdx1 promotes intestinal inflammation in CD at least in part by activating the NLRP3 inflammasome through lysosomal disruption in macrophages. These findings highlight the pathogenic role of Prdx1 in CD and reveal therapeutic potential of managing CD via neutralization of circulating Prdx1.