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Gliotoxin Protects Trinitrobenzene Sulfonic Acid-Induced Colonic Damage through Induction of Heme Oxygenase-1  

Oh, Jaemin (Wonkwang University School of Medicine and Institute of Medical Science)
Hur, Jungmu (Wonkwang University School of Medicine and Institute of Medical Science)
Kim, Yourim (Wonkwang University School of Medicine and Institute of Medical Science)
Kwon, Young-Mi (School of Oriental Medicine, Wonkwang University)
Kim, Kyungsuk (Wonkwang University School of Medicine and Institute of Medical Science)
Chung, Yeuntai (Wonkwang University School of Medicine and Institute of Medical Science)
Choi, Minkyu (Wonkwang University School of Medicine and Institute of Medical Science)
Publication Information
Toxicological Research / v.20, no.4, 2004 , pp. 293-298 More about this Journal
Abstract
Background: Crohn's disease is characterized by a chronic relapsing inflammation of the bowel. Gliotoxin has been known to play strong immunosuppressive properties, while mechanisms for its anti-inflammatory actions are not completely understood. Here, we investigated the effects of gliotoxin in trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, an animal model of Crohn's disease. Results: Gliotoxin dramatically improved clinical and histopathological symptoms in accompanied with reduced expression of TNF-$\alpha$, IL-1$\beta$, and ICAM-1 protein levels in TNBS induced colitis. Interestingly Gliotoxin induced Heme oxygenase-1 (HO-1) and the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) completely mimicked the protective effects of gliotoxin in TNBS induced colitis mice. In contrast, the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) could reverse the anti-inflammatory effects of gliotoxin and CoPPIX. Conclusions: Gliotoxin is a potential therapeutic agent targeting for the treatment of Crohn's disease by inducing HO-1.
Keywords
Gliotoxin; HO-1; TNBS colitis; Crohn's disease;
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