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Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury.

ABSTRACT: Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H₂S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H₂S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H₂S pretreatment. Moreover, H₂S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1? in the alveolar space. In vitro, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H₂S. Taken together, we provide first evidence that H₂S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H₂S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H₂S pretreatment ameliorates LPS-induced ALI.

SUBMITTER: Faller S

PROVIDER: S-EPMC6168479 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury.

Faller Simone S Hausler Florian F Goeft Andreas A von Itter Marc-Nicolas André MA Gyllenram Veronica V Hoetzel Alexander A Spassov Sashko G SG

Scientific reports 20181002 1

Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H<sub>2</sub>S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H<sub>2</sub>S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inf ...[more]

PMID: 30279441

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Project description:In addition to the lung, the liver is considered another major target for paraquat (PQ) poisoning. Hydrogen sulfide (H2S) has been demonstrated to be effective in the inhibition of oxidative stress and inflammation. The aim of this study was to investigate the protective effect of exogenous H2S against PQ-induced acute liver injury. The acute liver injury model was established by a single intraperitoneal injection of PQ, evidenced by histological alteration and elevated serum aminotransferase levels. Different doses of NaHS were administered intraperitoneally one hour before exposure to PQ. Analysis of the data shows that exogenous H2S attenuated the PQ-induced liver injury and oxidative stress in a dose-dependent manner. H2S significantly suppressed reactive oxygen species (ROS) generation and the elevation of malondialdehyde content while it increased the ratio of GSH/GSSG and levels of antioxidant enzymes including SOD, GSH-Px, HO-1, and NQO-1. When hepatocytes were subjected to PQ-induced oxidative stress, H2S markedly enhanced nuclear translocation of Nrf2 via S-sulfhydration of Keap1 and resulted in the increase in IDH2 activity by regulating S-sulfhydration of SIRT3. In addition, H2S significantly suppressed NLRP3 inflammasome activation and subsequent IL-1β excretion in PQ-induced acute liver injury. Moreover, H2S cannot reverse the decrease in SIRT3 and activation of the NLRP3 inflammasome caused by PQ in Nrf2-knockdown hepatocytes. In summary, H2S attenuated the PQ-induced acute liver injury by enhancing antioxidative capability, regulating mitochondrial function, and suppressing ROS-induced NLRP3 inflammasome activation. The antioxidative effect of H2S in PQ-induced liver injury can at least partly be attributed to the promotion of Nrf2-driven antioxidant enzymes via Keap1 S-sulfhydration and regulation of SIRT3/IDH2 signaling via Nrf2-dependent SIRT3 gene transcription as well as SIRT3 S-sulfhydration. Thus, H2S supplementation can form the basis for a promising novel therapeutic strategy for PQ-induced acute liver injury.

Dataset Information

Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury.

Publications

Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury.

Similar Datasets

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