IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration
IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration
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DOI：
10.1152/ajpgi.00513.2005
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发表时间：
2006-04-01
影响因子：
4.5
通讯作者：
Dambacher, J
中科院分区：
文献类型：
--
作者：
Brand, S;Beigel, F;Dambacher, J
IL-22在活动期克罗恩病中升高，并促进促炎基因表达和肠上皮细胞迁移。Am J Physiol Gasterintest liver Physiol290：G827-G838,2006年；DOI：10.1152/ajpgi.00513.2005。-IL-22由激活的T细胞产生，并通过由IL-22R1和IL-10R2组成的受体复合体发出信号。本研究的目的是分析肠上皮细胞(IEC)中IL-22受体的表达、信号转导以及该细胞因子系统的特定生物学功能。逆转录-聚合酶链式反应进行表达研究。用Western印迹实验分析细胞信号转导，用3-(4，5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(-2H-TTZ法检测细胞增殖，用流式细胞仪检测Fas诱导的细胞凋亡。损伤实验研究IEC的迁移情况。IEC株Caco-2、DLD-1、SW480、HCT116和HT-29均表达IL-22受体亚基IL-22R1和IL-10R2。经TNF-α、IL-1β和内毒素刺激后，IL-22R1的表达显著上调，但不影响IL-10R2的mRNA表达。IL-22与其受体复合体结合可激活STAT1/3、Akt、ERK1/2和SAPK/JNK的MAP激酶。IL-22显著促进细胞增殖(P=0.002)和磷脂酰肌醇3-激酶依赖的内皮细胞迁移(P=0.00001)以及肿瘤坏死因子-α、IL-8和人β-防御素-2mRNA的表达。IL-22对Fas诱导的细胞凋亡无影响。IL-22mRNA在克罗恩病患者炎性病变中的表达增加，且与IL-8的表达呈高度正相关(r=0.840)。此外，在葡聚糖硫酸钠诱导的小鼠结肠炎中，IL-22的表达增加。IEC表达IL-22的功能性受体，促进促炎细胞因子的表达，并通过增加防御素的表达促进先天免疫反应。此外，我们的数据表明这种细胞因子促进IEC迁移的肠道屏障功能，这表明在肠道炎症和伤口愈合中发挥重要作用。IL-22在活动期克罗恩病中升高，并促进促炎基因表达和IEC迁移。
IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 290: G827-G838, 2006; doi:10.1152/ajpgi.00513.2005.-IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2. The aim of this study was to analyze IL-22 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal epithelial cells (IEC). Expression studies were performed by RT-PCR. Signal transduction was analyzed by Western blot experiments, cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-( 4-sulfophenyl)-2H-tetrazolium assay and Fas-induced apoptosis by flow cytometry. IEC migration was studied in wounding assays. The IEC lines Caco-2, DLD-1, SW480, HCT116, and HT-29 express both IL-22 receptor subunits IL-22R1 and IL-10R2. Stimulation with TNF-alpha, IL-1 beta, and LPS significantly upregulated IL-22R1 without affecting IL-10R2 mRNA expression. IL-22 binding to its receptor complex activates STAT1/3, Akt, ERK1/2, and SAPK/JNK MAP kinases. IL-22 significantly increased cell proliferation ( P = 0.002) and phosphatidylinsitol 3-kinase-dependent IEC cell migration (P = 0.00001) as well as mRNA expression of TNF-alpha, IL-8, and human beta-defensin-2. IL-22 had no effect on Fas-induced apoptosis. IL-22 mRNA expression was increased in inflamed colonic lesions of patients with Crohn's disease and correlated highly with the IL-8 expression in these lesions (r = 0.840). Moreover, IL-22 expression was increased in murine dextran sulfate sodium-induced colitis. IEC express functional receptors for IL-22, which increases the expression of proinflammatory cytokines and promotes the innate immune response by increased defensin expression. Moreover, our data indicate intestinal barrier functions for this cytokine-promoting IEC migration, which suggests an important function in intestinal inflammation and wound healing. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and IEC migration.