An endogenously anti-inflammatory role for methylation in mucosal inflammation identified through metabolite profiling.
An endogenously anti-inflammatory role for methylation in mucosal inflammation identified through metabolite profiling.
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DOI：
10.4049/jimmunol.1002805
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Colgan SP
中科院分区：
文献类型：
--
作者：
Kominsky DJ;Keely S;MacManus CF;Glover LE;Scully M;Collins CB;Bowers BE;Campbell EL;Colgan SP
粘膜组织由提供屏障和运输功能的上皮细胞覆盖。现在认识到，IBD中的炎症反应伴随着组织代谢的显著变化。在这里，我们研究了全球代谢的粘膜炎症的后果，采用在体外和体内模型的疾病。在上皮模型和从鼠结肠炎分离的结肠组织中由炎症引起的代谢特征的初步分析表明，与细胞甲基化反应相关的特定代谢物的水平被模型炎症系统显著改变。此外，所有细胞甲基化的核心酶SAM合成酶和SAH水解酶的表达响应于炎症而增加。随后的研究表明，DNA甲基化在炎症过程中显著增加，并且在用可逆SAH水解酶抑制剂DZ 2002治疗后，上皮NF-κB活性显著抑制。最后，这些研究表明，在结肠炎的鼠模型中抑制细胞甲基化导致疾病恶化，而补充叶酸以促进甲基化部分改善了鼠结肠炎的严重程度。总之，这些结果确定了甲基化的整体变化，其在炎症期间转化为粘膜上皮的整体保护作用。
Tissues of the mucosa are lined by an epithelium that provides barrier and transport functions. It is now appreciated that inflammatory responses in IBD are accompanied by striking shifts in tissue metabolism. Here we examined global metabolic consequences of mucosal inflammation employing both in vitro and in vivo models of disease. Initial analysis of the metabolic signature elicited by inflammation in epithelial models and in colonic tissue isolated from murine colitis demonstrated that levels of specific metabolites associated with cellular methylation reactions are significantly altered by model inflammatory systems. Furthermore, expression of enzymes central to all cellular methylation, SAM synthetase and SAH hydrolase, are increased in response to inflammation. Subsequent studies showed that DNA methylation is substantially increased during inflammation and that epithelial NF-κB activity is significantly inhibited following treatment with a reversible SAH hydrolase inhibitor, DZ2002. Finally, these studies demonstrated that inhibition of cellular methylation in a murine model of colitis results in disease exacerbation while folate supplementation to promote methylation partially ameliorates the severity of murine colitis. Together, these results identify a global change in methylation, which during inflammation, translates to an overall protective role in mucosal epithelia.
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影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
影响因子：
15.9
作者：
Khoury, Joseph;Ibla, Juan C.;Colgan, Sean R.
通讯作者：
Colgan, Sean R.
DOI：
10.1073/pnas.0602235103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Cummins, Eoin P.;Berra, Edurne;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
影响因子：
4.8
作者：
Halim, AB;LeGros, L;Kotb, M
通讯作者：
Kotb, M
DOI：
10.1084/jem.193.9.1027
发表时间：
2001-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Furuta GT;Turner JR;Taylor CT;Hershberg RM;Comerford K;Narravula S;Podolsky DK;Colgan SP
通讯作者：
Colgan SP