Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice
Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice
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DOI：
10.1097/00042737-200206000-00005
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发表时间：
2002-06-01
影响因子：
2.1
通讯作者：
Babyatsky, MW
中科院分区：
文献类型：
--
作者：
Eliakim, R;Fan, QX;Babyatsky, MW
背景吸烟改变炎症性肠病的进程，与预防溃疡性结肠炎有关，但会加重或对克罗恩病没有影响。虽然这种差异的病因尚不清楚，但在这些研究中还没有研究溃疡性结肠炎和克罗恩病受累部位的差异。目的观察尼古丁对白介素10缺乏小鼠空肠炎和结肠炎病程的影响。方法雄性C57/BL10白介素10-/-和野生型小鼠在12-14周出现炎症性肠病临床症状时，在饮用水中给予尼古丁(12.5µg/ml)。性别和年龄匹配的对照组小鼠只喝自来水，治疗2周后全部处死。分离空肠、近端和远端结肠全组织切片，进行大体观察和组织学评分。Northern印迹法检测生长抑素、肠三叶因子和粘蛋白-2的表达。结果14~16周时，IL-10-/-对照组小鼠出现空肠炎(肉眼评分1.4+/-0.5，镜检评分2.0+/-0.2)和结肠炎(2.0+/-0.2和5.9+/-0.9)。用尼古丁治疗2周的IL-10-/-小鼠的结肠评分显著降低(分别为1.4+/-0.6和2.2+/-0.15)。空肠损伤较重(分别为2.6±0.4和4.0±0.3，P=0.01)。尼古丁显著增加结肠生长抑素和肠三叶因子的mRNA表达，但对空肠粘蛋白-2和β-肌动蛋白的表达无明显影响。结论(1)尼古丁两周给药对IL-10-/-小鼠空肠和结肠炎的影响不同。(2)尼古丁可减轻结肠炎症，其机制可能与促进两种保护性多肽的表达有关。《欧洲胃肠病杂志》14：607-614(C)2002里平科特·威廉姆斯·威尔金斯。
Background Cigarette smoking alters the course of inflammatory bowel disease, is associated with protection against ulcerative colitis, but aggravates or has no effect on Crohn's disease. While the aetiology of this discrepancy remains unclear, differences between location of involvement in ulcerative colitis and Crohn's disease have not been examined in these studies.Aim To examine the effects of nicotine administration on the course of jejunitis and colitis in interleukin-10 deficient mice.Methods Male C57/BL10 IL-10 -/- and wild type mice were given nicotine (12.5 mug/ml) in their drinking water at age 12-14 weeks when they had developed clinical signs of inflammatory bowel disease. Gender and age matched control mice received tap water alone, All mice were killed after 2 weeks of treatment. Whole tissue sections of jejunum, proximal and distal colon were separated and examined by macroscopic and histological score. Northern blots were examined for somatostatin, intestinal trefoil factor and mucin-2.Results At 14-16 weeks, when the mice were killed, IL-10 -/- untreated control mice developed jejunitis (macroscopic score 1.4 +/- 0.5, microscopic score 2.0 +/- 0.2) and colitis (2.0 +/- 0.2 and 5.9 +/- 0.9, respectively). IL-10 -/- mice treated for 2 weeks with nicotine had significantly reduced colonic scores (1.4 +/- 0.6 and 2.2 +/- 0.15, respectively). In contrast, the jejunum was more severely damaged (2.6 +/- 0.4 and 4.0 +/- 0.3; P = 0.01, respectively). Nicotine significantly increased both somatostatin and intestinal trefoil factor mRNA expression in the colon but not in the jejunum; no effect was noted on mucin-2 or beta-actin mRNA expression.Conclusions (1) Two weeks of nicotine administration leads to contrasting effects on jejunal and colonic inflammation in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was associated with enhanced expression of two protective peptides. Eur J Gastroenterol Hepatol 14:607-614 (C) 2002 Lippincott Williams Wilkins.