CORM-2 inhibits TXNIP/NLRP3 inflammasome pathway in LPS-induced acute lung injury

• DOI: 10.1007/s00011-016-0973-7
• Publication Date: 2016-07-13T11:46:22Z
• Authors: Lei Jiang; Dongsheng Fei; Rui Gong; Wei Yang; Wei Yu; Shangha Pan; Mingran Zhao; Mingyan Zhao
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Inflammasomes; Acute Lung Injury; Caspase 1; Interleukin-1beta; Anti-Inflammatory Agents; Interleukin-18; NF-kappa B; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Thioredoxins; NLR Family, Pyrin Domain-Containing 3 Protein; Organometallic Compounds; Animals; Carrier Proteins; Reactive Oxygen Species; Bronchoalveolar Lavage Fluid; Lung; Peroxidase; Signal Transduction

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-1β, 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-ΚB activity, and reactive oxygen species (ROS) production.LPS triggered significant lung edema, lung injury, and leukocyte infiltration, and elevated the levels of IL-1β and IL-18 in lung BAL fluids. CORM-2 pretreatment resulted in a marked amelioration of lung injury and reduced IL-1β 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-κB 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.