Regulation of sodium-glutamine cotransport in villus and crypt cells by glucocorticoids during chronic enteritis
Regulation of sodium-glutamine cotransport in villus and crypt cells by glucocorticoids during chronic enteritis
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DOI：
10.1002/ibd.22924
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Sundaram, Uma
中科院分区：
文献类型：
--
作者：
Arthur, Subha;Saha, Prosenjit;Sundaram, Uma
背景：肠上皮细胞对营养素的吸收主要由钠依赖性共转运（NGct）介导。绒毛细胞中主要的NGcT，B 0AT 1，在慢性肠道炎症期间被抑制继发于协同转运蛋白数量的减少。相比之下，在慢性回肠炎期间，由SN 2介导的隐窝细胞中的NGcT被刺激，继发于协同转运蛋白对谷氨酰胺的亲和力增加。糖皮质激素是治疗炎症性肠病的主要药物。然而，其对NGcT的影响尚不清楚。方法：用甲基强的松龙（MP）逆转慢性肠炎时绒毛细胞B 0AT 1的抑制。这是次要的刷状缘膜，而不是在亲和力的改变共转运蛋白的数量的恢复。慢性回肠炎期间隐窝细胞中NGcT的刺激也通过MP治疗恢复到其正常水平。这种逆转是次要的恢复改变亲和力的协同转运蛋白SN 2谷氨酰胺。结果：动力学研究和蛋白质印迹分析是一致的功能研究的两个协同转运。因此，糖皮质激素恢复两个独特的改变钠-谷氨酰胺共转运蛋白，B 0AT 1绒毛和SN 2的隐窝细胞在慢性肠炎。结论：这些数据表明，糖皮质激素作为一种上游广谱免疫调节剂在慢性炎症肠道。（Inflamm Bowel Dis 2012;）
Background: Assimilation of the preferred nutrient of enterocytes is mediated primarily by sodium (Na)-dependent cotransport (NGct) in the intestine. The predominant NGcT in villus cells, B0AT1, is inhibited secondary to a decrease in cotransporter numbers during chronic intestinal inflammation. In contrast, NGcT mediated by SN2 in crypt cells is stimulated secondary to increased affinity of the cotransporter for glutamine during chronic ileitis. Glucocorticoid is a mainstay of treatment for inflammatory bowel disease. However, its effect on NGcT is not known. Methods: The inhibition of B0AT1 in villus cells during chronic intestinal inflammation was reversed back to normal by methylprednisolone (MP). This was secondary to the restoration of the cotransporter numbers in the brush border membrane rather than an alteration in the affinity. The stimulation of NGcT in crypt cells during chronic ileitis was also restored back to its normal levels by MP treatment. This reversal was secondary to the restoration of the altered affinity of the cotransporter SN2 for glutamine. Results: Kinetic studies and western blot analysis were consistent with functional studies for both cotransporters. Thus, glucocorticoids restore two uniquely altered Na-glutamine cotransporters, B0AT1 in villus and SN2 in crypt cells during chronic enteritis. Conclusions: These data indicate that glucocorticoids function as an upstream broad spectrum immune modulator in the chronically inflamed intestine. (Inflamm Bowel Dis 2012;)