HMGB1 mediates lipopolysaccharide-induced macrophage autophagy and pyroptosis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2023-01-19 DOI:10.1186/s12860-023-00464-7
Jiawei Shang, Feng Zhao, Yongmei Cao, Feng Ping, Wei Wang, Yingchuan Li
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引用次数: 3

Abstract

Autophagy and pyroptosis of macrophages play important protective or detrimental roles in sepsis. However, the underlying mechanisms remain unclear. High mobility group box protein 1 (HMGB1) is associated with both pyroptosis and autophagy. lipopolysaccharide (LPS) is an important pathogenic factor involved in sepsis. Lentivirus-mediated HMGB1 shRNA was used to inhibit the expression of HMGB1. Macrophages were treated with acetylation inhibitor (AA) to suppress the translocation of HMGB1 from the nucleus to the cytosol. Autophagy and pyroptosis-related protein expressions were detected by Western blot. The levels of caspase-1 activity were detected and the rate of pyroptotic cells was detected by flow cytometry. LPS induced autophagy and pyroptosis of macrophages at different stages, and HMGB1 downregulation decreased LPS-induced autophagy and pyroptosis. Treatment with acetylation inhibitor (anacardic acid) significantly suppressed LPS-induced autophagy, an effect that was not reversed by exogenous HMGB1, suggesting that cytoplasmic HMGB1 mediates LPS-induced autophagy of macrophages. Anacardic acid or an anti-HMGB1 antibody inhibited LPS-induced pyroptosis of macrophages. HMGB1 alone induced pyroptosis of macrophages and this effect was inhibited by anti-HMGB1 antibody, suggesting that extracellular HMGB1 induces macrophage pyroptosis and mediates LPS-induced pyroptosis. In summary, HMGB1 plays different roles in mediating LPS-induced autophagy and triggering pyroptosis according to subcellular localization.

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HMGB1介导脂多糖诱导的巨噬细胞自噬和焦亡。
巨噬细胞的自噬和焦亡在脓毒症中起着重要的保护或有害作用。然而,潜在的机制仍不清楚。高迁移率组盒蛋白1 (HMGB1)与焦亡和自噬都有关。脂多糖(LPS)是脓毒症的重要致病因子。采用慢病毒介导的HMGB1 shRNA抑制HMGB1的表达。用乙酰化抑制剂(AA)处理巨噬细胞,抑制HMGB1从细胞核向胞浆的易位。Western blot检测细胞自噬和热噬相关蛋白的表达。用流式细胞术检测caspase-1活性水平和热噬细胞率。LPS在不同阶段诱导巨噬细胞自噬和焦亡,HMGB1下调可降低LPS诱导的自噬和焦亡。乙酰化抑制剂(心梗酸)显著抑制lps诱导的自噬,而外源性HMGB1不能逆转这一作用,提示胞质HMGB1介导lps诱导的巨噬细胞自噬。心梗酸或抗hmgb1抗体抑制lps诱导的巨噬细胞热亡。HMGB1单独诱导巨噬细胞热亡,抗HMGB1抗体可抑制这一作用,提示细胞外HMGB1诱导巨噬细胞热亡并介导lps诱导的热亡。综上所述,HMGB1在介导lps诱导的自噬和触发焦亡过程中,根据亚细胞定位的不同发挥着不同的作用。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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