Heme oxygenase-1 prevents murine intestinal inflammation

抄録

Heme oxygenases (HOs) are rate-limiting enzymes catabolizing heme to biliverdin, ferrous iron, and carbon monoxide, and of the three HO isoforms identified, HO-1 plays a protective role against inflammatory processes. In this study, we investigated the possible role of HO-1 in intestinal inflammation. Acute colitis was induced in male C57BL/6 (wild-type) and homozygous BTB and CNC homolog 1 (Bach1)-deficient mice, which show high HO-1 expression in the colonic mucosa, using dextran sodium sulfate. The disease activity index, myeloperoxidase activity, and inflammatory cytokines in the colonic mucosa were evaluated 7 days after dextran sodium sulfate-dependent colitis induction. We also evaluated the impact of HO-1 inhibition using zinc protoporphyrin IX (25 mg/kg i.p., daily). After dextran sodium sulfate administration, HO-1 mRNA and protein expression increased in a time-dependent manner. Disease activity index score, myeloperoxidase activity, and colonic production of TNF-α and IFN-γ were increased after dextran sodium sulfate administration, and co-administration of zinc protoporphyrin IX enhanced their increase. In addition, disease activity index in Bach1-deficient was significantly lower after dextran sodium sulfate administration than that in wild type mice. These results indicate that HO-1 plays a protective role against dextran sodium sulfate-induced intestinal inflammation, possibly by regulating pro-inflammatory cytokines in intestinal tissues.