Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells
Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells
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DOI：
10.1053/gast.2001.21188
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发表时间：
2001-02-01
期刊：
影响因子：
29.4
通讯作者：
Rafter, J
中科院分区：
文献类型：
--
作者：
Glinghammar, B;Rafter, J
背景和目的：越来越多的证据表明环氧合酶 (COX)-2 活性抑制剂可用于预防人类结肠癌。因此，确定结肠腔内容物中的物质是否可以影响结肠细胞中 COX-2 的转录调节非常重要。方法：使用人 COX-2 启动子-荧光素酶构建体在 HCT 116 细胞中进行瞬时转染，并研究纯管腔化合物和粪便水成分（与结肠细胞直接接触的粪便部分）对荧光素酶活性的影响。结果：管腔化合物脱氧胆酸盐、鹅脱氧胆酸盐和丁酸盐均诱导 HCT 116 细胞中的 COX-2 启动子活性。人类粪便水的脂质提取物也诱导这些细胞中的启动子活性，并且诱导程度因个体而异。脂质提取物对 COX-2 启动子活性的诱导与激活蛋白 1 依赖性基因转录的诱导呈正相关。结果还表明蛋白激酶 C 和 p38 丝裂原激活蛋白激酶介导管腔药物对 COX-2 启动子活性的影响。结论：管腔内容物中的成分可以影响COX-2转录并可能影响结肠肿瘤的发展。现有数据表明，负责的成分受到饮食的影响。
Background & Aims: Evidence is accumulating that inhibitors of cyclooxygenase (COX)-2 activity are useful for preventing human colon cancer. Therefore, it is important to determine whether agents in the colonic luminal contents can influence the transcriptional regulation of COX-2 in colonic cells. Methods: Transient transfections were performed, using a human COX-2 promoter-luciferase construct, in HCT 116 cells, and the effects of pure luminal compounds and components of fecal water, the fecal fraction in direct contact with the colonocytes, on luciferase activity studied. Results: The luminal compounds deoxycholate, chenodeoxycholate, and butyrate all induced COX-2 promoter activity in HCT 116 cells. Lipid extracts of human fecal water also induced promoter activity in these cells, and the extent of induction varied between individuals. Induction of COX-2 promoter activity by the lipid extracts was positively correlated with induction of activator protein 1-dependent gene transcription. Results also indicated that protein kinase C and p38 mitogen-activated protein kinase mediated the effect of the luminal agents bn COX-2 promoter activity. Conclusions: Components in the luminal contents can effect COX-2 transcription and may influence colonic tumor development. Available data suggest that the responsible components are under dietary influence.