title: Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation.
abstract: BACKGROUND
  Carbon monoxide (CO) released from CORM-2 has anti-inflammatory function, but the critical molecule mediating the inflammation inhibition has not been elucidated. Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating host defense against oxidative stress and inflammation-related disorders. In this study we use Nrf2 knockout mice to determine the role of Nrf2 in mediating the CO anti-inflammatory action.
  
  
  METHODS
  We compared CORM-2's inhibiting effect on pro-inflammatory cytokine expressions (TNF-α, IL-1β and IL-6 and iNOS) in primary peritoneal macrophages, mouse liver and brain tissues from Nrf2(+/+) and Nrf2(-/-) mice. We further assayed the inflammatory cell infiltration in both liver and brain tissues of the Nrf2(+/+) and Nrf2(-/-) mice. Finally, we examined CORM's influence on mouse mortality in a mouse sepsis model.
  
  
  RESULTS
  Our results showed that CORM-2 dramatically inhibited the expression of pro-inflammatory cytokines in Nrf2(+/+) mice, but not in Nrf2(-/-) mice. Furthermore CORM-2 substantially decreased LPS-induced mouse mortality of Nrf2(+/+) mice, but not of Nrf2(-/-) mice.
  
  
  CONCLUSIONS
  We conclude that Nrf2 is indispensable for CORM-2 inhibition of LPS-induced inflammation.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, School of Medicine and State Key Lab of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: SiYuan
authors.initials: S
authors.lastname: Qin
authors.forename: RongHui
authors.initials: R
authors.lastname: Du
authors.forename: ShaSha
authors.initials: S
authors.lastname: Yin
authors.forename: XinFeng
authors.initials: X
authors.lastname: Liu
authors.forename: GeLin
authors.initials: G
authors.lastname: Xu
authors.forename: Wangsen
authors.initials: W
authors.lastname: Cao
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D018805:Sepsis / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide