Nicotine ameliorates colonic inflammation via down-regulation of MAdCAM-1 expression on high endotherial venule like vessel.

Abstract

Background: Ulcerative colitis (UC) is an intractable colonic disease. Lymphocytes migration to colonic mucosa through endotherial venule like vessel is considered to be involved in pathophysiology of this disease. Anti-adhesion molecule therapy targeting MAdCAM-1 on high endotherial venule like vessel is one of the promising therapy. Smoking has been reported to have a beneficial effect on UC. Nevertheless, pathophysiology of nicotine on activity of UC is still to be elucidated. This time, we investigated the involvement of nicotine in the colonic inflammation using murine colitis model.

Method: In murine study, tissue samples were obtained from colon of C57BL/6J mouse provided with drinking water containing dextran sulfate sodium (DSS). Degree of mRNA expression of TNF-α and MAdCAM-1 was determined by using quantitative RT-PCR. The inhibitory effects of nicotine on activity of colitis and mRNA expression were determined. To induce high endothelial venules in vitro, bEnd3 cell line was treated with TNF-alpha. Effect of nicotine on MAdCAM-1 expression on high endothelial venule (HEV) like vessel was also measured by using quantitative RT-PCR.

Results: In murine colitis model, administration of nicotine ameliorated DSS colitis. Administration of nicotine also significantly decreased degree of expression of MAdCAM-1 mRNA on HEV-like vessel.

Conclusion: Nicotine ameliorates DSS colitis possibly via down regulation of MAdCAM-1 expression on HEV-like vessel, and accordingly, inhibition of aberrant lymphocyte migration in colonic mucosa.