Rebamipide Protects TNBS Induced Colonic Damage Through Down-regulation of NF-kappaB Activation and Induction of Heme Oxygenase -1 Expression.
- Author:
Jae Min OH
1
;
Jeong Re LEE
;
Young Mi KWON
;
Yu Rim KIM
;
Kyoung Suk KIM
;
Min Kyu CHOI
;
Yeun Tai CHUNG
Author Information
1. Department of Anatomy, School of Medicine, Wonkwang University and Wonkwang Medical Science Institute, Korea. mkchoi@wonkwang.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Rebamipide;
HO-1;
TNBS induced colitis;
Crohn's disease
- MeSH:
Cobalt;
Colitis;
Colon*;
Crohn Disease;
Cytokines;
Down-Regulation*;
Heme Oxygenase (Decyclizing)*;
Heme*;
HT29 Cells;
Humans;
Inflammation;
Intercellular Adhesion Molecule-1;
Interleukin-8;
NF-kappa B*;
Peroxidase;
Tumor Necrosis Factor-alpha;
Ulcer
- From:Korean Journal of Anatomy
2005;38(1):31-38
- CountryRepublic of Korea
- Language:English
-
Abstract:
Crohn 's disease is characterized by a chronic relapsing inflammation of the bowel in which pro-inflammatory cytokines play an important role. Rebamipide is an anti-gastric ulcer drug with anti-inflammatory properties in vivo and in vitro. The effects of rebamipide on Crohn 's disease have not been carefully evaluated. This study investigated the potential of rebamipide to protect Crohn 's disease using a murine model of colitis induced by trinitrobenzene sulfonic acid (TNBS). Rebamipide dramatically improved histopathological symptom involving myeloperoxidase (MPO)activation and increase of microscopic damage score in TNBS induced colitis. Rebamipide suppressed IL-8 secretion, ICAM-1 induction and nuclear factor-kappaB (NF-kappaB) activation by TNF-alpha and induced heme oxygenase-1(HO-1)in HT-29 cells. HO-1 inducer cobalt protoporphyrin IX (CoPPIX)suppressed NF-kappaB activation by TNF-alpha in HT-29 cells like rebamipide, and mimicked the protective effects of rebamipide on TNBS induced colitis. This suggests that rebamipide exerts anti-inflammatory effects by down-regulating NF-kappaB activity via inducting HO-1 expression. In conclusion, this study suggests that rebamipide represents a potential therapeutic agent and HO-1 is an important therapeutic target for the treatment of Crohn's disease.
