Cytokine regulation of OCTN2 expression and activity in small and large intestine.
Cytokine regulation of OCTN2 expression and activity in small and large intestine.
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DOI：
10.1002/ibd.21444
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发表时间：
2011-04
影响因子：
4.9
通讯作者：
Chang, Eugene B.
中科院分区：
文献类型：
--
作者：
Fujiya, Mikihiro;Inaba, Yuhei;Musch, Mark W.;Hu, Shien;Kohgo, Yutaka;Chang, Eugene B.
关键词：
有机阳离子转运蛋白 OCTN2 位于 IBD5 风险等位基因上，与炎症性肠病 (IBD) 的发病机制有关。 OCTN2 在顶膜中表达，并转运许多溶质，包括可能参与宿主-微生物相互作用的细菌衍生介质。为了进一步探讨其作用，我们研究了人类 IBD 和 OCTN2 表达实验模型中的潜在调节因素。人结肠上皮细胞 (Caco2BBE) 用于研究炎症介质对 OCTN2 活性和表达的影响。通过表面生物素化评估 OCTN2 的顶膜表达。 Rag-1−/−缺陷小鼠用于确定适应性免疫细胞在调节 OCTN2 表达中的潜在作用。用细胞因子 IFN-γ 和 TNF-α 处理 C57Bl/6 小鼠，以确定对 OCTN2 表达和活性的影响。通过蛋白质印迹和免疫组织化学评估人类 IBD 标本中的 OCTN2 表达。 OCTN2 活性和表达受肠道炎症状态调节。 Rag-1−/− 缺陷小鼠结肠组织中的 OCTN2 表达降低。 IFN-γ和TNF-α治疗增加了肠道OCTN2表达，特别是在结肠中。 IFN-γ增加Caco2BBE OCTN2的总膜表达和顶膜表达，而TNF-α刺激顶膜表达。克罗恩病和溃疡性结肠炎的炎症活跃区域的结肠上皮 OCTN2 表达增加。肠上皮 OCTN2 表达因肠道炎症而增加，很可能是通过促炎细胞因子水平增加而增加。这些发现表明 OCTN2 可能参与炎症相关应激条件下肠道稳态的恢复。
The organic cation transporter OCTN2 is located on the IBD5 risk allele and has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). OCTN2 is expressed in the apical membrane and transports many solutes including bacteria-derived mediators that may be involved in host-microbial interactions. To explore its role further, we examined potential regulatory factors in human IBD and in experimental models on OCTN2 expression. Human colonic epithelial cells (Caco2BBE) were used to investigate effects of inflammatory mediators on OCTN2 activity and expression. Apical membrane expression of OCTN2 was assessed by surface biotinylation. Rag-1−/−deficient mice were used to determine the potential role of adaptive immune cells in the regulation of OCTN2 expression. C57Bl/6 mice were treated with the cytokines, IFN-γ and TNF-α, to determine effects on OCTN2 expression and activity. OCTN2 expression in human IBD specimens was assessed by Western blotting and immunohistochemistry. OCTN2 activity and expression are regulated by the state of intestinal inflammation. OCTN2 expression in colonic tissues of Rag-1−/− deficient mice was reduced. Treatment with IFN-γ and TNF-α increased intestinal OCTN2 expression, particularly in the colon. IFN-γ increased both total and apical membrane expression of Caco2BBE OCTN2, whereas TNF-α stimulated apical expression. Colonic epithelial OCTN2 expression was increased in actively inflamed areas of both Crohn’s disease and ulcerative colitis. Intestinal epithelial OCTN2 expression is increased by intestinal inflammation, most likely through increased levels of proinflammatory cytokines. These findings suggest OCTN2 may participate to restoration of intestinal homeostasis under conditions of inflammation-associated stress.
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影响因子：
15.9
作者：
MADARA, JL;STAFFORD, J
通讯作者：
STAFFORD, J
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Merlin D