title: Carbon monoxide attenuates dextran sulfate sodium-induced colitis via inhibition of GSK-3β signaling.
abstract: Endogenous carbon monoxide (CO) is produced by heme oxygenase-1 (HO)-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3β in mice model. To support the in vivo observation, TNF-α, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs) and bone marrow-derived macrophages (BMMs) from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3β activation and decreased TNF-α and iNOS expression by inhibition of NF-κB activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3β signaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3β in DSS-induced colitis model.
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: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Sun-oh
authors.initials: SO
authors.lastname: Jeong
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea ; Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Yanbian University, Yanji 133000, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
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 Anatomy, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
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
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D002248:Carbon Monoxide; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3