Heme oxygenase-1: a new therapeutic target for inflammatory bowel disease.
Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). Three mammalian HO isozymes have been identified, one of which, HO-1, is a stress-responsive protein induced by various oxidative agents. HO-2 and HO-3 genes are constitutively expressed. Recent studies demonstrate that the expression of HO-1 in response to different inflammatory mediators may contribute to the resolution of inflammation and have protective effects in several organs against oxidative injury. Although the mechanism underlying the anti-inflammatory actions of HO-1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the intestinal tract, HO-1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. Recent studies suggest that the induction of HO-1 expression plays a critical protective role in intestinal damage models induced by trinitrobenzene sulphonic acid or dextran sulphate sodium, indicating that activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the intestinal tract. These in vitro and in vivo data suggest that HO-1 may be a novel therapeutic target in patients with inflammatory bowel disease.
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. ynaito@koto.kpu-m.ac.jp
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Naito
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Takagi
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Yoshikawa
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001663:Bilirubin / Q000378:metabolism; D001664:Biliverdine / Q000378:metabolism; D002248:Carbon Monoxide / Q000502:physiology; D003106:Colon / Q000201:enzymology; D016207:Cytokines / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000627:therapeutic use*; D051547:Heme Oxygenase-1; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000201:enzymology; D008565:Membrane Proteins
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008565:Membrane Proteins; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine; D001663:Bilirubin