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