Peroxiredoxin 1 mediates bleomycin-induced acute lung injury in mice via macrophage NOD1/NF-κB axis.

BACKGROUND: Bleomycin (BLM), a widely used antitumor drug, has been demonstrated to induce pulmonary toxicity in both chemotherapy patients and experimental animals, leading to acute lung injury (ALI). However, the lack of effective treatment options limits its clinical application. While peroxiredoxin 1 (Prdx1), a novel damage-associated molecular pattern (DAMP), has been shown to exacerbate acute liver and kidney injury by promoting inflammatory responses, its role in BLM-induced ALI remains unclear. METHODS: An ALI mouse model was established via intratracheal instillation of BLM (5 mg/kg). Prdx1 gene-knockout mice, recombinant murine Prdx1 protein (rPrdx1), and Prdx1-neutralizing monoclonal antibody were utilized to investigate the role of Prdx1 in BLM-induced ALI. Further mechanistic insights were explored through single-cell RNA sequencing analysis. RESULTS: BLM-induced damage to bronchial epithelial cells triggered Prdx1 release, which subsequently activated the NOD1/NF-κB signaling pathway in macrophages, promoting the release of inflammatory cytokines and exacerbating pulmonary inflammation and pathological damage. These findings were confirmed by single-cell RNA sequencing. Genetic knockout of Prdx1 or administration of Prdx1-neutralizing monoclonal antibody protected mice from BLM-induced ALI, and this protective effect was attenuated by introducing rPrdx1. CONCLUSION: These findings identify Prdx1 as a potential therapeutic target for BLM-induced ALI, offering a strategy to mitigate its pulmonary toxicity and facilitate the broader clinical application of BLM.