Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a chronic and recurrent inflammatory disorder of the intestinal tract. Since the precise pathogenesis of IBD remains unclear, it is important to investigate the pathogenesis of IBD and to evaluate new anti-inflammatory strategies. Recent evidence suggests that heme oxygenase-1 (HO-1) plays a critical protective role during the development of intestinal inflammation. In fact, it has been demonstrated that the activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in various animal intestinal injury models induced by ischemia-reperfusion, indomethacin, lipopolysaccharide-associated sepsis, trinitrobenzene sulfonic acid or dextran sulfate sodium. In addition, carbon monoxide (CO) derived from HO-1 has been shown to be involved in the regulation of intestinal inflammation. Furthermore, administration of a low concentration of exogenous CO has a protective effect against intestinal inflammation. These data suggest that HO-1 and CO may be novel therapeutic molecules for patients with gastrointestinal inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 and CO in intestinal inflammation.
Keywords: HEME OXYGENASE, CARBON MONOXIDE, INFLAMMATORY BOWEL DISEASE
Full Text
The Full Text of this article is available as a PDF (117.7 KB).
References
- 1.Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T. Prevalence of ulcerative colitis and Crohn's disease in Japan. J Gastroenterol 2009; 44: 659–665. [DOI] [PubMed] [Google Scholar]
- 2.Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417–429. [DOI] [PubMed] [Google Scholar]
- 3.Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448: 427–434. [DOI] [PubMed] [Google Scholar]
- 4.Naito Y, Takagi T, Yoshikawa T. Heme oxygenase-1: a new therapeutic target for inflammatory bowel disease. Aliment Pharmacol Ther 2004; 20 (Suppl 1): 177–184. [DOI] [PubMed] [Google Scholar]
- 5.Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997; 37: 517–554. [DOI] [PubMed] [Google Scholar]
- 6.Sassa S. Biological implications of heme metabolism. J Clin Biochem Nutr 2006; 38: 138–155. [Google Scholar]
- 7.Shibahara S. Regulation of heme oxygenase gene expression. Semin Hemato11988; 25: 370-376. [PubMed] [Google Scholar]
- 8.Igarashi K, Sun J. The heme-Bachl pathway in the regulation of oxidative stress response and erythroid differentiation. Antioxid Redox Signal 2006; 8: 107–118. [DOI] [PubMed] [Google Scholar]
- 9.Morse D, Lin L, Choi AM, Ryter SW Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease. Free Radic Biol Med 2009; 47: 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Morse D, Choi AM. Heme oxygenase-1: from bench to bedside. Am J Respir Crit Care Med 2005; 172: 660–670. [DOI] [PubMed] [Google Scholar]
- 11.Otterbein LE, Soares MP, Yamashita K, Bach FH. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 2003; 24: 449–455. [DOI] [PubMed] [Google Scholar]
- 12.Otterbein LE, Mantell LL, Choi AM. Carbon monoxide provides protection against hyperoxic lung injury. Am J Pathol 1999; 276: L688–L694. [DOI] [PubMed] [Google Scholar]
- 13.Kaizu T, Ikeda A, Nakao A et al. Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation. Am J Physiol 2008; 294: G236–G244. [DOI] [PubMed] [Google Scholar]
- 14.Kaizu T, Nakao A, Tsung A et al. Carbon monoxide inhalation ameliorates cold ischemia/reperfusion injury after rat liver transplantation. Surgery 2005; 138: 229–235. [DOI] [PubMed] [Google Scholar]
- 15.Nakao A, Kimizuka K, Stolz DB et al. Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury. Am J Pathol 2003; 163: 1587–1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Nakao A, Toyokawa H, Abe M et al. Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and alloreactive T-cell responses. Transplantation 2006; 81: 220–230. [DOI] [PubMed] [Google Scholar]
- 17.Neto JS, Nakao A, Kimizuka K et al. Protection of transplant-induced renal ischemia-reperfusion injury with carbon monoxide. Am J Physiol 2004; 287: F979–F989. [DOI] [PubMed] [Google Scholar]
- 18.Takagi T, Naito Y, Inoue M et al. Inhalation of carbon monoxide ameliorates collagen-induced arthritis in mice and regulates the articular expression of IL-lbeta and MCP-1. Inflammation 2009; 32: 83–88. [DOI] [PubMed] [Google Scholar]
- 19.Tsui TY, Obed A, Siu YT et al. Carbon monoxide inhalation rescues mice from fulminant hepatitis through improving hepatic energy metabolism. Shock 2007; 27: 165–171. [DOI] [PubMed] [Google Scholar]
- 20.Hegazi RA, Rao KN, Mayle A, Sepulveda AR, Otterbein LE, Plevy SE. Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J Exp Med 2005; 202: 1703–1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Takagi T, Naito Y, Mizushima K et al. Inhalation of carbon monoxide ameliorates TNBS-induced colitis in mice through the inhibition of TNF-alpha expression. Dig Dis Sci 2010; In press.
- 22.Zuckerbraun BS, Otterbein LE, Boyle P et al. Carbon monoxide protects against the development of experimental necrotizing enterocolitis. Am J Physiol 2005; 289: G607–G613. [DOI] [PubMed] [Google Scholar]
- 23.Takagi T, Naito Y, Mizushima K et al. Increased intestinal expression of heme oxygenase-1 and its localization in patients with ulcerative colitis. J Gastroenterol Hepatol 2008; 23 (Suppl 2): S229–S233. [DOI] [PubMed] [Google Scholar]
- 24.Takagi T, Naito Y, Tsuboi H et al. Increased intestinal luminal carbon monoxide gas in patients with ulcerative colitis Aliment Pharmacol Ther 2006; 24 (Suppl 4): 233–238. [Google Scholar]
- 25.Maestrelli P, El Messlemani AH, Fina De 0 et al. Increased expression of heme oxygenase (H0)-1 in alveolar spaces and HO-2 in alveolar walls of smokers. Am J Respir Crit Care Med 2001; 164: 1508–1513. [DOI] [PubMed] [Google Scholar]
- 26.Yoshiki N, Kubota T, Aso T. Identification of heme oxygenase in human endometrium. J Clin Endocrinol Metab 2001; 86: 5033–5038. [DOI] [PubMed] [Google Scholar]
- 27.Barton SG, Rampton DS, Winrow VR, Domizio P, Feakins RM. Expression of heat shock protein 32 (hemoxygenase-1) in the normal and inflamed human stomach and colon: an immunohistochemical study. Cell Stress Chaperones 2003; 8: 329–334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Paul G, Bataille F, Obermeier F et al. Analysis of intestinal haem-oxygenase-1 (H0-1) in clinical and experimental colitis. Clin Exp Immunol. 2005; 140: 547–555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Miller SM, Reed D, Sarr MG, Farrugia G, Szurszewski JH. Haem oxygenase in enteric nervous system of human stomach and jejunum and co-localization with nitric oxide synthase. Neurogastroenterol Motil 2001; 13: 121–131. [DOI] [PubMed] [Google Scholar]
- 30.Ny L, Alm P, Larsson B, Andersson KE. Morphological relations between haem oxygenases, NO-synthase and VIP in the canine and feline gastrointestinal tracts. J Auton Nerv Syst 1997; 65: 49–56. [DOI] [PubMed] [Google Scholar]
- 31.Farrugia G, Miller SM, Rich A et al. Distribution of heme oxygenase and effects of exogenous carbon monoxide in canine jejunum. Am J Physiol 1998; 274: G350–G358. [DOI] [PubMed] [Google Scholar]
- 32.Grozdanovic Z, Gossrau R. Expression of heme oxygenase-2 (HO-2)-like immunoreactivity in rat tissues. Acta Histochem 1996; 98: 203–214. [DOI] [PubMed] [Google Scholar]
- 33.Hu Y, Yang M, Ma N, Shinohara H, Semba R. Contribution of carbon monoxide-producing cells in the gastric mucosa of rat and monkey. Histochem Cell Biol 1998; 109: 369–373. [DOI] [PubMed] [Google Scholar]
- 34.Ny L, Alm P, Ekstrom P, Larsson B, Grundemar L, Andersson KE. Localization and activity of haem oxygenase and functional effects of carbon monoxide in the feline lower oesophageal sphincter. Br J Pharmacol 1996; 118: 392-399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Attuwaybi B, Kozar RA, Gates KS et al. Hypertonic saline prevents inflammation, injury, and impaired intestinal transit after gut ischemia/reperfusion by inducing heme oxygenase 1 enzyme. J Trauma 2004; 56: 749–758, discussion 58-59. [DOI] [PubMed] [Google Scholar]
- 36.Attuwaybi BO, Hassoun HT, Zou L et al. Hypothermia protects against gut ischemia/reperfusion-induced impaired intestinal transit by inducing heme oxygenase-1. J Surg Res 2003; 115: 48–55. [DOI] [PubMed] [Google Scholar]
- 37.Attuwaybi BO, Kozar RA, Moore-Olufemi SD et al. Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury. J Surg Res 2004; 118: 53–57. [DOI] [PubMed] [Google Scholar]
- 38.Mallick IH, Winslet MC, Seifalian AM. Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection. Am J Surg 2010; 199: 223–231. [DOI] [PubMed] [Google Scholar]
- 39.Mallick IH, Yang W, Winslet MC, Seifalian AM. Protective effects of ischemic preconditioning on the intestinal mucosal microcirculation following ischemia-reperfusion of the intestine. Microcirculation 2005; 12: 615–625. [DOI] [PubMed] [Google Scholar]
- 40.Mallick IH, Yang WX, Winslet MC, Seifalian AM. Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine. World J Gastroenterol 2005; 11: 7308–7313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Sakamoto N, Kokura S, Okuda T et al. Heme oxygenase-1 (Hsp32) is involved in the protection of small intestine by whole body mild hyperthermia from ischemia/reperfusion injury in rat. Int J Hyperthermia 2005; 21: 603–614. [DOI] [PubMed] [Google Scholar]
- 42.Tamaki T, Konoeda Y, Yasuhara M et al. Glutamine-induced heme oxygenase-1 protects intestines and hearts from warm ischemic injury. Transplant Proc 1999; 31: 1018–1019. [DOI] [PubMed] [Google Scholar]
- 43.Wasserberg N, Pileggi A, Salgar SK et al. Heme oxygenase-1 upregulation protects against intestinal ischemia/reperfusion injury: a laboratory based study. Int J Surg 2007; 5: 216–224. [DOI] [PubMed] [Google Scholar]
- 44.Harusato A, Naito Y, Takagi T et al. Inhibition of Bachl ameliorates indomethacin-induced intestinal injury in mice. J Physiol Pharmacol 2009; 60 (Suppl 7): 149–154. [PubMed] [Google Scholar]
- 45.Higuchi K, Yoda Y, Amagase K et al. Prevention of NSAID-induced small intestinal mucosal injury: prophylactic potential of lansoprazole. J Clin Biochem Nutr 2009; 45: 125–130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Pang Q, Ji Y, Li Y, Bermudez-Humaran LG, Hu G, Zeng Y. Intragastric administration with recombinant Lactococcus lactis producing heme oxygenase-1 prevents lipopolysaccharide-induced endotoxemia in rats. FEMS Microbiol Lett 2008; 283: 62–68. [DOI] [PubMed] [Google Scholar]
- 47.Ping W, Qizi Y, Hesheng O, Lijia T, Jun Y, Chaoshu T. Endogenous heme oxygenase/carbon monoxide system mediates lipopolysaccharide-induced intussusception in rats. Chin Med Sci J 2000; 15: 89–92. [PubMed] [Google Scholar]
- 48.Tamion F, Richard V, Renet S, Thuillez C. Protective effects of heme-oxygenase expression against endotoxic shock: inhibition of tumor necrosis factor-alpha and augmentation of interleukin-10. J Trauma 2006; 61: 1078–1084. [DOI] [PubMed] [Google Scholar]
- 49.Tamion F, Richard V, Renet S, Thuillez C. Intestinal preconditioning prevents inflammatory response by modulating heme oxygenase-1 expression in endotoxic shock model. Am J Physiol 2007; 293: G1308–G1314. [DOI] [PubMed] [Google Scholar]
- 50.Uehara K, Takahashi T, Fujii H et al. The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury. Crit Care Med 2005; 33: 381–390. [DOI] [PubMed] [Google Scholar]
- 51.Abbasoglu SD, Erbil Y, Eren T et al. The effect of heme oxygenase-1 induction by octreotide on radiation enteritis. Peptides 2006; 27: 1570–1576. [DOI] [PubMed] [Google Scholar]
- 52.Gins M, Erbil Y, Oztezcan S et al. The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis. Am J Surg 2006; 191: 503–509. [DOI] [PubMed] [Google Scholar]
- 53.Hsu JT, Kan WH, Hsieh CH et al. Mechanism of estrogen-mediated intestinal protection following trauma-hemorrhage: p38 MAPK-dependent upregulation of HO-1. Am J Physiol 2008; 294: R1825–R1831. [DOI] [PubMed] [Google Scholar]
- 54.Pang QF, Ji Y, Bermudez-Humaran LG, Zhou QM, Hu G, Zeng Y. Protective effects of a heme oxygenase- 1 -secreting Lactococcus lactis on mucosal injury induced by hemorrhagic shock in rats. J Surg Res 2009; 153: 39–45. [DOI] [PubMed] [Google Scholar]
- 55.Tamion F, Richard V, Bonmarchand G, Leroy J, Lebreton JP, Thuillez C. Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock. Am J Respir Crit Care Med 2001; 164: 1933–1938. [DOI] [PubMed] [Google Scholar]
- 56.Tamion F, Richard V, Lacoume Y, Thuillez C. Intestinal preconditioning prevents systemic inflammatory response in hemorrhagic shock. Role of HO-1. Am J Physiol 2002; 283: G408–G414. [DOI] [PubMed] [Google Scholar]
- 57.Umeda K, Takahashi T, Inoue K et al. Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase-1 induction. Shock 2009; 31: 40–49. [DOI] [PubMed] [Google Scholar]
- 58.Gan HT, Chen JD. Induction of heme oxygenase-1 improves impaired intestinal transit after burn injury. Surgery 2007; 141: 385–393. [DOI] [PubMed] [Google Scholar]
- 59.Li X, Schwacha MG, Chaudry IH, Choudhry MA. Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47phox and p67phox activity and 02- production in a two-hit model of alcohol intoxication and burn injury. J Immunol 2008; 180: 6933–6940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Gins M, Erbil Y, Dogru-Abbasoglu S et al. The effect of heme oxygenase-1 induction by glutamine on TNBS-induced colitis. The effect of glutamine on TNBS colitis. Int J Colorectal Dis 2007; 22: 591–599. [DOI] [PubMed] [Google Scholar]
- 61.Coeffier M, Le Pessot F, Leplingard A etal. Acute enteral glutamine infusion enhances heme oxygenase-1 expression in human duodenal mucosa. J Nutr 2002; 132: 2570–2573. [DOI] [PubMed] [Google Scholar]
- 62.Wang WP, Guo X, Koo MW et al. Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats. Am J Physiol 2001; 281: G586–G594. [DOI] [PubMed] [Google Scholar]
- 63.Naito Y, Takagi T, Tomatsuri N. Role of heme oxygenase-1 in dextran sulfate sodium-induced intestinal inflammation in mice. Gastroenterology 2003; 124 (Suppl): A-490. [Google Scholar]
- 64.Takagi T, Naito Y, Katada K. Heme oxygenase regulates the balance of inflammatory cytokines in dextran sulfate sodium-induced colitis. Gastroenterology 2004; 126 (Suppl): A-564. [Google Scholar]
- 65.Berberat PO, AR YI, Yamashita K et al. Heme oxygenase- 1 - generated biliverdin ameliorates experimental murine colitis. Inflamm Bowel Dis 2005; 11: 350–359. [DOI] [PubMed] [Google Scholar]
- 66.Sun X, Suzuki K, Nagata M et al. Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase-1. Pathol Int 2010; 60: 93–101. [DOI] [PubMed] [Google Scholar]
- 67.Zhong W, Xia Z, Hinrichs D etal. Hemin exerts multiple protective mechanisms and attenuates dextran sulfate sodium-induced colitis. J Pediatr Gastroenterol Nutr 2010; 50: 132–139. [DOI] [PubMed] [Google Scholar]
- 68.Erbil Y, Gins M, Abbasoglu SD et al. Effect of heme oxygenase-1 induction by octreotide on TNBS-induced colitis. J Gastroenterol Hepatol 2007; 22: 1852–1858. [DOI] [PubMed] [Google Scholar]
- 69.Horvath K, Varga C, Berko A, Posa A, Laszlo F, Whittle BJ. The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis. Eur J Pharmacol 2008; 581: 315–323. [DOI] [PubMed] [Google Scholar]
- 70.Jun CD, Kim Y, Choi EY et al. Gliotoxin reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice: evidence of the connection between heme oxygenase-1 and the nuclear factor-kappaB pathway in vitro and in vivo. Inflamm Bowel Dis 2006; 12: 619–629. [DOI] [PubMed] [Google Scholar]
- 71.Lee SH, Sohn DH, Jin XY, Kim SW, Choi SC, Seo GS. 2',4',6'-Tris(methoxymethoxy) chalcone protects against trinitrobenzene sulfonic acid-induced colitis and blocks tumor necrosis factor-alpha-induced intestinal epithelial inflammation via heme oxygenase 1-dependent and independent pathways. Biochem Pharmacol 2007; 74: 870–880. [DOI] [PubMed] [Google Scholar]
- 72.Varga C, Laszlo F, Fritz P et al. Modulation by heme and zinc protoporphyrin of colonic heme oxygenase-1 and experimental inflammatory bowel disease in the rat. Eur J Pharmacol 2007; 561: 164–171. [DOI] [PubMed] [Google Scholar]
- 73.Brusko TM, Wasserfall CH, Agarwal A, Kapturczak MH, Atkinson MA. An integral role for heme oxygenase-1 and carbon monoxide in maintaining peripheral tolerance by CD4+CD25+ regulatory T cells. J Immunol 2005; 174: 5181–5186. [DOI] [PubMed] [Google Scholar]
- 74.George JF, Braun A, Brusko TM et al. Suppression by CD4*CD25* regulatory T cells is dependent on expression of heme oxygenase-1 in antigen-presenting cells. Am J Pathol 2008; 173: 154–160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75.Croog VJ, Ullman TA, Itzkowitz SH. Chemoprevention of colorectal cancer in ulcerative colitis. Int J Colorectal Dis 2003; 18: 392–400. [DOI] [PubMed] [Google Scholar]
- 76.Nakao A, Kaczorowski DJ, Sugimoto R, Billiar TR, McCurry KR. Application of heme oxygenase-1, carbon monoxide and biliverdin for the prevention of intestinal ischemia/reperfusion injury. J Clin Biochem Nutr 2008; 42: 78–88. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 77.Alonso JR, Cardellach F, Lopez S, Casademont J, Miro O.. Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain. Pharmacol Toxicol 2003; 93: 142–146. [DOI] [PubMed] [Google Scholar]
- 78.Zuckerbraun BS, Chin BY, Bilban M et al. Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species. FASEB J 2007; 21: 1099–1106. [DOI] [PubMed] [Google Scholar]
- 79.Taille C, El-Benna J, Lanone S, Boczkowski J, Motterlini R. Mitochondrial respiratory chain and NAD(P)H oxidase are targets for the antiproliferative effect of carbon monoxide in human airway smooth muscle. J Biol Chem 2005; 280: 25350–25360. [DOI] [PubMed] [Google Scholar]
- 80.Nakao A, Faleo G, Shimizu H et al. Ex vivo carbon monoxide prevents cytochrome P450 degradation and ischemia/reperfusion injury of kidney grafts. Kidney Int 2008; 74: 1009–1016. [DOI] [PubMed] [Google Scholar]
- 81.Kajimura M, Fukuda R, Bateman RM, Yamamoto T, Suematsu M. Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H(2)S gas biology. Antioxid Redox Signal 2010; In press. [DOI] [PMC free article] [PubMed]
- 82.Denninger JW, Marletta MA. Guanylate cyclase and the NO/cGMP signaling pathway. Biochim Biophys Acta 1999; 1411: 334–350. [DOI] [PubMed] [Google Scholar]
- 83.Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP. Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol 2000; 184: 409–420. [DOI] [PubMed] [Google Scholar]
- 84.Liu H, Mount DB, Nasjletti A, Wang W Carbon monoxide stimulates the apical 70-pS IC' channel of the rat thick ascending limb. J Clin Invest 1999; 103: 963–970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85.Brouard S, Otterbein LE, Anrather J et al. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 2000; 192: 1015–1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86.Brouard S, Berberat PO, Tobiasch E, Seldon MP, Bach FH, Soares MP. Heme oxygenase- 1 -derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J Biol Chem 2002; 277: 17950–17961. [DOI] [PubMed] [Google Scholar]
- 87.Zhang X, Shan P, Otterbein LE et al. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J Biol Chem 2003; 278: 1248–1258. [DOI] [PubMed] [Google Scholar]
- 88.Otterbein LE, Bach FH, Alam J et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000; 6: 422–428. [DOI] [PubMed] [Google Scholar]
- 89.Sarady JK, Otterbein SL, Liu F, Otterbein LE, Choi AM. Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Am J Respir Cell Mol Biol 2002; 27: 739–745. [DOI] [PubMed] [Google Scholar]
- 90.Reed JA, Whitsett JA. Granulocyte-macrophage colony-stimulating factor and pulmonary surfactant homeostasis. Proc Assoc Am Phys 1998; 110: 321–332. [PubMed] [Google Scholar]
- 91.Liu SH, Ma K, Xu B, Xu XR. Protection of carbon monoxide intraperitoneal administration from rat intestine injury induced by lipopolysaccharide. Chin Med J ( Engl) 2010; 123: 1039–1046. [PubMed] [Google Scholar]
- 92.Liu SH, Ma K, Xu XR, Xu B. A single dose of carbon monoxide intraperitoneal administration protects rat intestine from injury induced by lipopolysaccharide. Cell Stress Chaperones 2010; In press. [DOI] [PMC free article] [PubMed]
- 93.Liu SH, Xu XR, Ma K, Xu B. Protection of carbon monoxide inhalation on lipopolysaccharide-induced multiple organ injury in rats. Chin Med Sci J2007; 22: 169-176. [PubMed] [Google Scholar]
- 94.De Backer O, Elinck E, Blanckaert B, Leybaert L, Motterlini R, Lefebvre RA. Water-soluble CO-releasing molecules reduce the development of postoperative ileus via modulation of MAPK/H0-1 signalling and reduction of oxidative stress. Gut 2009; 58: 347–356. [DOI] [PubMed] [Google Scholar]
- 95.Moore BA, Otterbein LE, Turler A, Choi AM, Bauer AJ. Inhaled carbon monoxide suppresses the development of postoperative ileus in the murine small intestine. Gastroenterology 2003; 124: 377–391. [DOI] [PubMed] [Google Scholar]
- 96.Moore BA, Overhaus M, Whitcomb Jet al. Brief inhalation of low-dose carbon monoxide protects rodents and swine from postoperative ileus. Crit Care Med 2005; 33: 1317–1326. [DOI] [PubMed] [Google Scholar]
- 97.Nakao A, Schmidt J, Harada T etal. A single intraperitoneal dose of carbon monoxide-saturated Ringer's lactate solution ameliorates postoperative ileus in mice. J Pharmacol Exp Ther 2006; 319: 1265–1275. [DOI] [PubMed] [Google Scholar]
- 98.Nakao A, Kimizuka K, Stolz DB et al. Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts. Surgery 2003; 134: 285–292. [DOI] [PubMed] [Google Scholar]
- 99.Nakao A, Moore BA, Murase N et al. Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility. Gut 2003; 52: 1278–1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 100.Nakao A, Toyokawa H, Tsung A et al. Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury. Am J Transplant 2006; 6: 2243–2255. [DOI] [PubMed] [Google Scholar]
- 101.Guo Y, Stein AB, Wu WJ et al. Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo. Am J Physiol 2004; 286: H1649–H1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 102.Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE, Green CJ. Carbon monoxide-releasing molecules: characterization of biochemical and vascular activities. Circ Res 2002; 90: E17–E24. [DOI] [PubMed] [Google Scholar]
- 103.Clark JE, Naughton P, Shurey Set al. Cardioprotective actions by a water-soluble carbon monoxide-releasing molecule. Circ Res 2003; 93: e2–e8. [DOI] [PubMed] [Google Scholar]
- 104.Sun B, Sun Z, Jin Q, Chen X. CO-releasing molecules (CORM-2)-liberated CO attenuates leukocytes infiltration in the renal tissue of thermally injured mice. Int J Biol Sci 2008; 4: 176–183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 105.Vera T, Henegar JR, Drummond HA, Rimoldi JM, Stec DE. Protective effect of carbon monoxide-releasing compounds in ischemia-induced acute renal failure. J Am Soc Nephrol 2005; 16: 950–958. [DOI] [PubMed] [Google Scholar]
- 106.Cepinskas G, Katada K, Bihari A, Potter RE Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice. Am J Physiol 2008; 294: G184–G191. [DOI] [PubMed] [Google Scholar]
- 107.Sun BW, Chen ZY, Chen X, Liu C. Attenuation of leukocytes sequestration by carbon monoxide-releasing molecules: liberated carbon monoxide in the liver of thermally injured mice. J Burn Care Res 2007; 28: 173–181. [DOI] [PubMed] [Google Scholar]
- 108.Sun B, Sun H, Liu C, Shen J, Chen Z, Chen X. Role of CO-releasing molecules liberated CO in attenuating leukocytes sequestration and inflammatory responses in the lung of thermally injured mice. J Surg Res 2007; 139: 128–135. [DOI] [PubMed] [Google Scholar]
- 109.Chen P, Sun B, Chen H etal. Effects of carbon monoxide releasing molecule-liberated CO on severe acute pancreatitis in rats. Cytokine 2010; 49: 15–23. [DOI] [PubMed] [Google Scholar]
- 110.Katada K, Bihari A, Mizuguchi Set al. Carbon monoxide liberated from CO-releasing molecule (CORM-2) attenuates ischemia/reperfusion (I/R)-induced inflammation in the small intestine. Inflammation 2010; 33: 92–100. [DOI] [PubMed] [Google Scholar]
- 111.Liu DM, Sun BW, Sun ZW, Jin Q, Sun Y, Chen X. Suppression of inflammatory cytokine production and oxidative stress by CO-releasing molecules-liberated CO in the small intestine of thermally-injured mice. Acta Pharmacol Sin 2008; 29: 838–846. [DOI] [PubMed] [Google Scholar]
- 112.Boyko EJ, Koepsell TD, Perera DR, Inui TS. Risk of ulcerative colitis among former and current cigarette smokers. N Engl J Med 1987; 316: 707–710. [DOI] [PubMed] [Google Scholar]
- 113.de Saussure P, Clerson P, Prost PL, Truong Tan N, Bouhnik Y, Appendectomy Gil R., smoking habits and the risk of developing ulcerative colitis: a case control study in private practice setting. Gastroenterol Clin Biol 2007; 31: 493–497. [DOI] [PubMed] [Google Scholar]
- 114.Jick H, Walker AM. Cigarette smoking and ulcerative colitis. N Engl J Med 1983; 308: 261–263. [DOI] [PubMed] [Google Scholar]
- 115.Okamoto R, Watanabe M. Cellular and molecular mechanisms of the epithelial repair in IBD. Dig Dis Sci 2005; 50 (Suppl 1): S34–S38. [DOI] [PubMed] [Google Scholar]
- 116.Uchiyama K, Naito Y, Takagi T et al. Carbon monoxide enhance colonic epithelial restitution via FGF15 derived from colonic myofibroblasts. Biochem Biophys Res Commun 2010; 391: 1122–1126. [DOI] [PubMed] [Google Scholar]
- 117.Mayr FB, Spiel A, Leitner J et al. Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med 2005; 171: 354–360. [DOI] [PubMed] [Google Scholar]
- 118.Bathoorn E, Slebos DJ, Postma DS et al. Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study Eur Respir J2007; 30: 1131-1137. [DOI] [PubMed] [Google Scholar]