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Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy?mediated NLRP3 inflammasome inactivation in sepsis.

ABSTRACT: Sepsis is a highly heterogeneous syndrome that is caused by a dysregulated host response to infection. The disproportionate inflammatory response to invasive infection is a triggering event inducing sepsis. The activation of in?ammasomes in sepsis can amplify in?ammatory responses. It has been reported that damaged mitochondria contribute to NACHT, LRR and PYD domains?containing protein 3 (NLRP3) inflammasome?related sepsis. Our previous study revealed that hydrogen (H2) exerts anti?inflammatory effects in sepsis but the detailed mechanism remains to be elucidated. In the present study, septic mice induced by cecal ligation and puncture (CLP) and macrophages induced by lipopolysaccharide (LPS) were used as models of sepsis in vivo and in vitro, respectively. An inducer and inhibitor of autophagy and the NLRP3 inflammasome were administered to investigate the detailed mechanism of action of H2 treatment in sepsis. The results demonstrated that LPS and ATP led to NLRP3 inflammasome pathway activation, excessive cytokine release, mitochondrial dysfunction and the activation of autophagy. CLP induced organ injury and NLRP3 pathway activation. H2 treatment ameliorated vital organ damage, the inflammatory response, mitochondrial dysfunction and NLRP3 pathway activation, and promoted autophagy in macrophages induced by LPS and in CLP mice. However, the inhibitor of autophagy and the inducer of NLRP3 reversed the protective effect of H2 against organ damage, the inflammatory response and mitochondrial dysfunction in vivo and in vitro. Collectively, the results demonstrated that H2 alleviated mitochondrial dysfunction and cytokine release via autophagy?mediated NLRP3 inflammasome inactivation.

SUBMITTER: Chen H

PROVIDER: S-EPMC6713420 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy‑mediated NLRP3 inflammasome inactivation in sepsis.

Chen Hongguang H Mao Xing X Meng Xiaoyin X Li Yuan Y Feng Jingcheng J Zhang Linlin L Zhang Yang Y Wang Yaoqi Y Yu Yonghao Y Xie Keliang K

International journal of molecular medicine 20190813 4

Sepsis is a highly heterogeneous syndrome that is caused by a dysregulated host response to infection. The disproportionate inflammatory response to invasive infection is a triggering event inducing sepsis. The activation of inﬂammasomes in sepsis can amplify inﬂammatory responses. It has been reported that damaged mitochondria contribute to NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome‑related sepsis. Our previous study revealed that hydrogen (H2) exerts anti‑inflammatory ...[more]

PMID: 31432098

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Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy?mediated NLRP3 inflammasome inactivation in sepsis.

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Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy‑mediated NLRP3 inflammasome inactivation in sepsis.

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