Korean J Anat.  2004 Oct;37(5):459-466.

CoPPIX Protects against TNBS Induced Colitis Through HO-1 Induction

• Oh J
• Kim J
• Kwon YM
• Rheu M
• Kim Y
• Kim K
• Park S
• Kim J
• Choi M
• Chung Y

Abstract

Crohn`s disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is a need to develop new drugs for treating this disease that have few side effects. Heme oxygenase-1 (HO-1) has immunosuppressive properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects of HO-1 on trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. An HO-1 inducer, cobalt protoporphyrin IX (CoPPIX), dramatically improved the clinical and histopathological symptoms in TNBS-induced colitis. CoPPIX suppressed tumor necrosis factor-alpha and interleukin-1beta expression and down-regulated the nuclear transcription factor kappa B activity caused by TNBS. The vehicle copper protoporphyrin IX (CuPPIX) failed to duplicate the protective effects seen with CoPPIX. Moreover, an inhibitor of HO-1 activity-zinc protoporphyrin IX-reversed the protective effects of CoPPIX on TNBS-induced colitis. In conclusion CoPPIX protects against TNBS-induced colonic damage by inducing HO-1, which might be an important target in the treatment of Crohn`s disease.

Keyword

CoPPIX; HO-1; NF kappa B; TNBS colitis; Crohn`s disease

MeSH Terms

Animals
Cobalt
Colitis*
Colon
Copper
Heme Oxygenase-1
Immunosuppression
Inflammation
Interleukin-1beta
Mice
Transcription Factors
Tumor Necrosis Factor-alpha
Cobalt
Copper
Heme Oxygenase-1
Interleukin-1beta
Transcription Factors
Tumor Necrosis Factor-alpha