CoPPIX Protects against TNBS Induced Colitis Through HO-1 Induction

국문 초록 (Abstract)

크론병은 만성 염증성 대장 질환으로 면역반응을 억제함으로써 치료를 시도하고 있으나 치료가 쉽지 않고 치료하는 과정에서 많은 부작용이 생기는 질환이다. 따라서 부작용이 적은 새로운 약제의 개발이 절실한 실정이다. HO-1는 염증 반응을 억제하는 효과가 있다고 알려져 있으나 크론병에서의 그 작용기전은 거의 알려져 있지 않다. 따라서 우리는 크론병 동물모델인 TNBS에 의해 유도된 만성 대장염 모델에서 HO-1의 항 염증 기전을 조사하였다.
HO-1의 유도제인 CoPPIX 는 생쥐에서 TNBS에 의한 체중감소, MPO 활성, NF-κB 활성 및 병리, 조직학적 증상 등을 현
저히 개선하였다. 또한 염증의 유지에 중요한 역할을 하는 TNF-α와 IL-1β 등의 발현 역시 억제하였다. 이러한 CoPPIX의 효과들은 HO-1 활성 억제제인 ZnPPIX에 의해 차단되었다. 이상의 결과로 CoPPIX는 HO-1의 유도를 통해서 TNBS에 의해 유도된 만성 대장염의 증상들을 개선시킬 수 있다고 생각되었다.
결론적으로 CoPPIX는 크론병의 치료에 있어 중요한 치료제가 될 수 있다고 생각하며 HO-1은 크론병의 치료에 중요한
target 물질이 될 수 있다고 생각한다.

다국어 초록 (Multilingual 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-α and interleukin-1β expression and
down-regulated the nuclear transcription factor κB 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.

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