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Suppressive effect of nicotine on expression of MAdCAM‐1 in colitis
Author(s) -
Maruta Koji,
Kurihara Chie,
Furuhashi Hirotaka,
Takajo Takeshi,
Yasutake Yuichi,
Okada Yoshikiyo,
Yoshikawa Kenichi,
Higashiyama Masaaki,
Watanabe Chikako,
Komoto Shunsuke,
Tomita Kengo,
Nagao Shigeaki,
Miura Soichiro,
Hokari Ryota
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1023.5
Subject(s) - colitis , cell adhesion molecule , nicotine , inflammatory bowel disease , ulcerative colitis , medicine , splenocyte , immunology , adhesion , addressin , intravital microscopy , pharmacology , pathology , integrin , chemistry , immune system , receptor , disease , organic chemistry , microcirculation
Adhesion molecules play important roles in inflammatory bowel disease (IBD), and modulation of gut‐specific adhesion molecules like MAdCAM‐1 and α4β7‐integrin could be a new therapeutic target. Epidemically, nicotine absorbed by smoking is reported to work protectively in some ulcerative colitis cases. We investigated the effect of nicotine on dextran sulfate sodium (DSS)‐induced murine colitis in point of adhesion molecules. Aim We investigated the effect of nicotine on the following things; 1) symptoms of murine colitis; 2) leukocyte adhesion to colonic microvascular endothelium; 3) expression of α4β7‐integrin on lymphocytes; and 4) expression of adhesion molecules on endothelium. Method 1) C57BL/6J mice were treated with 3% DSS (40kDa) in drinking water for 7 days. Some mice were treated with 0.1 mg/ml nicotine in drinking water simultaneously. Disease activities of colitis were assessed by DAI score, which consists of body weight loss, stool consistency and bleeding. 2) C57BL/6J mice were treated with 0.1mg/ml nicotine in drinking water 1 day after 3% DSS treatment for 7 days. Mice were injected FITC‐labeld splenocytes (3×10 7 dissoleved in 0.3ml) obtained from another mouse, via cervical vein. The number of splenocytes adhering to colonic submucosal vasculature were counted with an intravital fluorescence microscope. 3) C57BL/6J mice were treated with 0.1mg/ml nicotine in drinking water 1 day or for 7 days. The expression of α4β7‐integrin on splenocytes was analyzed with a flow cytometer. 4) The bEnd.3 cells, a cell line derived from murine endothelioma, were treated with 5 ng/ml TNF‐α for 12 hours. Some groups were treated with 1 mM nicotine simultaneously. The mRNA expression of MAdCAM‐1 was measured by quantitative RT‐PCR. Result Nicotine treatment significantly decreased DAI score induced by DSS. In intravital microscopic study, the number of splenocytes adhering to vascular endothelium was increased by DSS treatment, and the increase was significantly attenuated by additional nicotine treatment. Expression of α4β7‐integrin on splenocytes was not affected by nicotine. In bEnd.3 cells, nicotine treatment significantly attenuated the increased expression of MAdCAM‐1 induced by TNF‐α. Conclusion Enhanced expression of adhesion molecules, especially MAdCAM‐1, on the microvascular endothelium in inflamed condition, was significantly inhibited by nicotine‐treatment. This study showed that nicotine might have a protective effect on inflammation of colonic mucosa of IBD via modulation of expression of MAdCAM‐1. Support or Funding Information None