title: CORM-2 inhibits TXNIP/NLRP3 inflammasome pathway in LPS-induced acute lung injury.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  CORM-2 suppresses TXNIP/NLRP3 inflammasome pathway and protects against LPS-induced lung injury.
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fei
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gong
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: The Key Hepatosplenic Surgery Laboratory, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Pediatrics, Children's Hospital of Harbin City, Harbin, China.
authors.forename: Mingran
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China. mingyan1970@126.com.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C445672:Txnip protein, mouse; C447082:tricarbonyldichlororuthenium (II) dimer; D013879:Thioredoxins; D009195:Peroxidase; D020170:Caspase 1
keywords: Acute lung injury; Carbon monoxide; NLRP3 inflammasome; TXNIP