Journal
INFLAMMATION RESEARCH
Volume 65, Issue 11, Pages 905-915Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-016-0973-7
Keywords
Carbon monoxide; Acute lung injury; NLRP3 inflammasome; TXNIP
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Funding
- National Natural Scientific Foundation of China [81171785]
- Natural Scientific Foundation of Heilongjiang Province [ZJY0704-02]
- Graduate Innovative Research Program of Harbin Medical University [YJSCX2015-21HYD]
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Accumulated studies suggest that exogenously administered carbon monoxide is beneficial for the resolution of acute lung inflammation. The present study aimed to examine the effects and the underlying mechanisms of CORM-2 on thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was intratracheally induced by LPS in C57BL6 mice. CORM-2 or iCORM-2 (30mg/kg i.p.) was administered immediately before LPS instillation. 6 h later, lung bronchoalveolar lavage (BAL) fluids were acquired for IL-18, IL-1 beta, and cell measurement, and lung issues were collected for histologic examination, wet/dry weight ratio, and determination of TXNIP/NLRP3 inflammasome expression, NLRP3 inflammasome and NF-IeB activity, and reactive oxygen species (ROS) production. LPS triggered significant lung edema, lung injury, and leukocyte infiltration, and elevated the levels of IL-1 beta and IL-18 in lung BAL fluids. CORM-2 pretreatment resulted in a marked amelioration of lung injury and reduced IL-1 beta and IL-18 secretion in BAL fluids. In lung tissues; CORM-2 down-regulated mRNA and protein level of TXNIP, NLRP3, ASC, and caspase-1. Furthermore, CORM-2 reduced ROS production, inhibited NLRP3 inflammasome and NF-kappa B activity, and interaction of TXNIP-NLRP3. However, no significant differences were detected between the LPS and iCORM-2 (an inactive variant of CORM-2) group. CORM-2 suppresses TXNIP/NLRP3 inflammasome pathway and protects against LPS-induced lung injury.
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