NOD3 Reduces Sepsis-Induced Acute Lung Injury by Regulating the Activation of NLRP3 Inflammasome and the Polarization of Alveolar Macrophages.

IF 4.5 2区 医学 Q2 CELL BIOLOGY
Yue Zhao, Yongran Wu, Lianlian Qu, Yingying Hu, Shengwen Sun, Ruishan Yao, Ruiting Li
{"title":"NOD3 Reduces Sepsis-Induced Acute Lung Injury by Regulating the Activation of NLRP3 Inflammasome and the Polarization of Alveolar Macrophages.","authors":"Yue Zhao, Yongran Wu, Lianlian Qu, Yingying Hu, Shengwen Sun, Ruishan Yao, Ruiting Li","doi":"10.1007/s10753-024-02197-x","DOIUrl":null,"url":null,"abstract":"<p><p>The pathogenesis of sepsis-induced Acute lung injury (ALI) progresses rapidly, and no effective treatment drugs are known, resulting in a high mortality rate. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation plays an important role in the pathological progression of ALI, and often coincide with the inflammatory activation and polarization of macrophages. NLR family CARD domain-containing protein 3 (NOD3) was reported protecting against sepsis-induced pulmonary pathological injury and inhibiting the inflammatory response in lung tissue. NOD3 can also inhibit NLRP3 inflammasome activation by competitively inhibiting the binding of pro-caspase-1 to apoptosis-related ASC or reducing NLRP3/cryopyrin-induced ASC speckle formation. In this study, we aimed to explore whether NOD3 decrease sepsis-induced lung injury by interfering with NLRP3 inflammasome activation and regulating alveolar macrophages (AMs) polarization. To investigate whether NOD3 reduce sepsis-induced ALI by inhibiting the activation of NLRP3 inflammasome to regulate the polarization of AMs. Sepsis-induced WT (C57BL/6) and NLRC3<sup>-</sup><sup>/</sup><sup>-</sup>-C57BL/6 mice ALI models were established by intraperitoneal injection of lipopolysaccharide (LPS). In vitro experiments, AMs and bone marrow-derived macrophages (BMDMs) were isolated from WT and NLRC3<sup>-</sup><sup>/</sup><sup>-</sup> mice. Using in vivo and in vitro experiments, we found that NOD3 knockout promoted the sepsis-induced inflammatory response in lung tissue. In addition, NOD3 knockout promoted the activation of the TRAF6-NF-κB signaling pathway and the NLRP3 inflammasome in AMs, enhanced the M1-type polarization of AMs and decreased the M2-type polarization of AMs in sepsis-induced lung injury model mice. NOD3 interfered with NLRP3 inflammasome activation by inhibiting NLRP3 inflammasome assembly or negatively regulating the TRAF6-NF-κB signaling pathway, and regulating the polarization of AMs, thereby alleviating sepsis-induced lung injury.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10753-024-02197-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The pathogenesis of sepsis-induced Acute lung injury (ALI) progresses rapidly, and no effective treatment drugs are known, resulting in a high mortality rate. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation plays an important role in the pathological progression of ALI, and often coincide with the inflammatory activation and polarization of macrophages. NLR family CARD domain-containing protein 3 (NOD3) was reported protecting against sepsis-induced pulmonary pathological injury and inhibiting the inflammatory response in lung tissue. NOD3 can also inhibit NLRP3 inflammasome activation by competitively inhibiting the binding of pro-caspase-1 to apoptosis-related ASC or reducing NLRP3/cryopyrin-induced ASC speckle formation. In this study, we aimed to explore whether NOD3 decrease sepsis-induced lung injury by interfering with NLRP3 inflammasome activation and regulating alveolar macrophages (AMs) polarization. To investigate whether NOD3 reduce sepsis-induced ALI by inhibiting the activation of NLRP3 inflammasome to regulate the polarization of AMs. Sepsis-induced WT (C57BL/6) and NLRC3-/--C57BL/6 mice ALI models were established by intraperitoneal injection of lipopolysaccharide (LPS). In vitro experiments, AMs and bone marrow-derived macrophages (BMDMs) were isolated from WT and NLRC3-/- mice. Using in vivo and in vitro experiments, we found that NOD3 knockout promoted the sepsis-induced inflammatory response in lung tissue. In addition, NOD3 knockout promoted the activation of the TRAF6-NF-κB signaling pathway and the NLRP3 inflammasome in AMs, enhanced the M1-type polarization of AMs and decreased the M2-type polarization of AMs in sepsis-induced lung injury model mice. NOD3 interfered with NLRP3 inflammasome activation by inhibiting NLRP3 inflammasome assembly or negatively regulating the TRAF6-NF-κB signaling pathway, and regulating the polarization of AMs, thereby alleviating sepsis-induced lung injury.

NOD3通过调节NLRP3炎性体的激活和肺泡巨噬细胞的极化,减轻脓毒症诱导的急性肺损伤。
脓毒症引起的急性肺损伤(ALI)的发病机制进展迅速,目前尚无有效的治疗药物,死亡率高。NLR家族pyrin domain containing 3 (NLRP3)炎性小体激活在ALI的病理进展中起重要作用,且常与巨噬细胞的炎症激活和极化相吻合。据报道,NLR家族CARD结构域蛋白3 (NOD3)对脓毒症诱导的肺病理损伤具有保护作用,并抑制肺组织的炎症反应。NOD3还可以通过竞争性抑制前caspase-1与凋亡相关的ASC结合或减少NLRP3/cryopyrin诱导的ASC斑点形成来抑制NLRP3炎性小体的激活。在本研究中,我们旨在探讨NOD3是否通过干扰NLRP3炎性体激活和调节肺泡巨噬细胞(AMs)极化来减轻败血症诱导的肺损伤。探讨NOD3是否通过抑制NLRP3炎性小体的激活来调节am的极化,从而减少败血症诱导的ALI。通过腹腔注射脂多糖(LPS)建立脓毒症诱导的WT (C57BL/6)和NLRC3-/—C57BL/6小鼠ALI模型。在体外实验中,从WT和NLRC3-/-小鼠中分离出AMs和骨髓源性巨噬细胞(bmdm)。通过体内和体外实验,我们发现NOD3敲除可促进脓毒症诱导的肺组织炎症反应。此外,敲除NOD3可促进脓毒症肺损伤模型小鼠AMs中TRAF6-NF-κB信号通路和NLRP3炎性小体的激活,增强AMs的m1型极化,降低AMs的m2型极化。NOD3通过抑制NLRP3炎性小体组装或负调控TRAF6-NF-κB信号通路,调控AMs的极化,从而干扰NLRP3炎性小体的激活,从而减轻败血症诱导的肺损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
文献相关原料
公司名称
产品信息
索莱宝
Penicillin-Streptomycin Liquid (PSL)
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信