Carbon Monoxide Liberated from Carbon Monoxide-Releasing Molecule Exerts an Anti-inflammatory Effect on Dextran Sulfate Sodium-Induced Colitis in Mice
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Tomohisa Takagi Yuji Naito Kazuhiko Uchiyama Takahiro Suzuki Ikuhiro Hirata Katsura Mizushima Hisato Tsuboi Natsuko Hayashi Osamu Ha
- چاپ و سال / کشور: 2010
Description
Background Endogenous carbon monoxide (CO) is one of the three products of heme degradation by heme oxygenase- 1 (HO-1) and exerts novel anti-inflammatory and anti-apoptotic effects as a gaseous second messenger. The purpose of this investigation was to determine whether exogenous CO could modulate intestinal inflammation. Methods Acute colitis was induced with 2% DSS in male C57BL/6 mice. CO-releasing molecule-2 (CORM-2; tricarbonyldichlororuthenium( II) dimer) was intraperitoneally administered twice daily and the disease activity index (DAI) was determined. We measured tissue-associated myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and the production of keratinocyte chemoattractant (KC) and tumor necrosis factor-a (TNF-a) protein in the intestinal mucosa. In an in-vitro study, young adult mouse colonic epithelial (YAMC) cells were incubated with TNF-a, and KC mRNA/protein expression and nuclear translocation of nuclear factor-kappa B (NF-jB) were measured with or without CORM-2 treatment. Results After DSS administration, DAI score increased in a time-dependent manner, and this increase was ameliorated by CORM-2 treatment. Increases in MPO activity and in the production of KC and TNF-a after DSS administration were significantly inhibited by CORM-2. TNF-ainduced KC production in YAMC cells was also inhibited by CORM-2 treatment. Further, nuclear translocation of NF-jB in YAMC cells was inhibited by CORM-2. Conclusion CORM-liberated CO significantly inhibited inflammatory response in murine colitis by inhibition of cytokine production in the colonic epithelium. These results suggest that CO could become a new therapeutic molecule for inflammatory bowel disease.
Dig Dis Sci (2011) 56:1663–1671 DOI 10.1007/s10620-010-1484-y Received: 18 March 2010 / Accepted: 2 November 2010 / Published online: 18 November 2010
