title: Carbon Monoxide Inhibits Tenascin-C Mediated Inflammation via IL-10 Expression in a Septic Mouse Model.
abstract: Tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, is specifically induced upon tissue injury and infection and during septic conditions. Carbon monoxide (CO) gas is known to exert various anti-inflammatory effects in various inflammatory diseases. However, the mechanisms underlying the effect of CO on TN-C-mediated inflammation are unknown. In the present study, we found that treatment with LPS significantly enhanced TN-C expression in macrophages. CO gas, or treatment with the CO-donor compound, CORM-2, dramatically reduced LPS-induced expression of TN-C and proinflammatory cytokines while significantly increased the expression of IL-10. Treatment with TN-C siRNA significantly suppressed the effects of LPS on proinflammatory cytokines production. TN-C siRNA did not affect the CORM-2-dependent increase of IL-10 expression. In cells transfected with IL-10 siRNA, CORM-2 had no effect on the LPS-induced expression of TN-C and its downstream cytokines. These data suggest that IL-10 mediates the inhibitory effect of CO on TN-C and the downstream production of proinflammatory cytokines. Additionally, administration of CORM-2 dramatically reduced LPS-induced TN-C and proinflammatory cytokines production while expression of IL-10 was significantly increased. In conclusion, CO regulated IL-10 expression and thus inhibited TN-C-mediated inflammation in vitro and in vivo.
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Md Jamal
authors.initials: MJ
authors.lastname: Uddin
authors.affiliation: Department of Pharmacology, Dalian University Medical college, Dalian, Liaoning 133000, China.
authors.forename: Chun-Shi
authors.initials: CS
authors.lastname: Li
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Yingqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Dalian University Medical college, Dalian, Liaoning 133000, China.
authors.forename: Qinggao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, New York-Presbyterian Hospital, and Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical Center, New York, NY 10065, USA.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Ryter
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000502:physiology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000188:drug therapy*; D019063:Tenascin / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D019063:Tenascin; D016753:Interleukin-10; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse