Korean J Anat.  2005 Feb;38(1):31-38.

Rebamipide Protects TNBS Induced Colonic Damage Through Down-regulation of NF-kappaB Activation and Induction of Heme Oxygenase -1 Expression

• Oh JM
• Lee JR
• Kwon YM
• Kim YR
• Kim KS
• Choi MK
• Chung YT

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.

Keyword

Rebamipide; HO-1; TNBS induced colitis; Crohn's disease

MeSH Terms

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
Cobalt
Cytokines
Heme
Heme Oxygenase (Decyclizing)
Intercellular Adhesion Molecule-1
Interleukin-8
NF-kappa B
Peroxidase
Tumor Necrosis Factor-alpha