BTB and CNC homology 1 (BACH1) plays a crucial role in the pathogenesis of acute lung injury (ALI) caused by gram-negative bacteria. However, its exact mechanisms in Staphylococcus aureus (SA)-induced ALI, a gram-positive bacterial infection, remain incompletely understood. In this study, we generated a BACH1-knockout mouse model (BACH1−/−) to investigate the role of BACH1 and its underlying mechanisms in regulating the development of sepsis-induced acute lung injury (ALI). Elevated levels of BACH1 were observed in both serum samples from septic patients and mouse models. Deletion of BACH1 alleviated ALI symptoms induced by sepsis. In bone marrow-derived macrophages, BACH1 deletion or knockdown suppressed NF-κB p65 phosphorylation and the induction of pro-inflammatory cytokines. Mechanistic studies demonstrated that BACH1 downregulated tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) mRNA expression by binding to its promoter region. These findings uncover inhibiting BACH1 may be a promising therapeutic strategy for treating gram-positive bacteria-induced ALI

中文翻译：

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BTB 和 CNC 同源性 1 的缺失可防止金黄色葡萄球菌诱导的急性肺损伤


BTB 和 CNC 同源性 1 （BACH1） 在革兰氏阴性菌引起的急性肺损伤 （ALI） 的发病机制中起关键作用。然而，它在金黄色葡萄球菌 （SA） 诱导的 ALI（一种革兰氏阳性细菌感染）中的确切机制仍不完全清楚。在这项研究中，我们生成了 BACH1 敲除小鼠模型 （BACH1-/-），以研究 BACH1 及其潜在机制在调节脓毒症诱导的急性肺损伤 （ALI） 发展中的作用。在脓毒症患者和小鼠模型的血清样本中均观察到 BACH1 水平升高。BACH1 的缺失减轻了脓毒症诱导的 ALI 症状。在骨髓来源的巨噬细胞中，BACH1 缺失或敲低抑制了 NF-κB p65 磷酸化和促炎细胞因子的诱导。机制研究表明，BACH1 通过结合其启动子区域下调肿瘤坏死因子-α 诱导的蛋白 3 （TNFAIP3） mRNA 表达。这些发现揭示了抑制 BACH1 可能是治疗革兰氏阳性菌诱导的 ALI 的一种有前途的治疗策略