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KMID : 0379520040200040293
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한국독성학회지
2004 Volume.20 No. 4 p.293 ~ p.298
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Gliotoxin Protects Trinitrobenzene Sulfonic Acid-Induced Colonic Damage through Induction of Heme Oxygenase-1
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Oh Jay-Min
Hur Jung-Mu
Kim You-Rim
Kwon Young-Mi
Kim Kyung-Suk
Chung Yeun-Tai
Choi Min-Kyu
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Abstract
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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-1beta, 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.
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KEYWORD
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Gliotoxin, HO-1, TNBS colitis, Crohn’s disease
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