Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells
Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells
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DOI：
10.1053/gast.2001.20914
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发表时间：
2001-01-01
期刊：
影响因子：
29.4
通讯作者：
Kagnoff, MF
中科院分区：
文献类型：
--
作者：
Dwinell, MB;Lügering, N;Kagnoff, MF
背景和目标：人肠上皮细胞可诱导表达中性粒细胞和单核细胞趋化因子，但对肠上皮细胞调节T细胞趋化因子的产生知之甚少。IP-10、Mig和I-TAG是3种CXC趋化因子，已知其充当CD 4（+）T细胞化学引诱物。我们研究了人结肠组织中趋化因子的组成性表达，并通过逆转录聚合酶链反应、酶联免疫吸附试验、以及使用培养的人肠上皮细胞系的免疫组织学和体内人肠异种移植模型的新适应。结果如下：IP-10和Mig由正常人结肠上皮组成性表达，其同源受体CXCR 3由粘膜单核细胞表达。干扰素（IFN）-γ刺激增加了人结肠上皮细胞系的这些趋化因子的mRNA表达和极化基底外侧分泌;肠侵袭性细菌感染或促炎细胞因子肿瘤坏死因子或白细胞介素1a刺激强烈增强IFN-γ诱导的上皮细胞IP-10、Mig和I-TAG产生。在人肠异种移植物中，IP-10、Mig和I-TAG的上皮细胞mRNA和蛋白表达响应于单独的IFN-γ或与IL-1组合的刺激而迅速上调。IFN-γ诱导的趋化因子IP-10、Mig和I-TAG通过人肠上皮的组成性和调节性产生，以及它们的同源受体CXCR 3的表达，提示肠上皮细胞在调节生理和病理性T细胞介导的粘膜炎症中发挥作用。
Background & Aims: Human intestinal epithelial cells inducibly express neutrophil and monocyte chemoattractants, yet little is known about the regulated production of T-cell chemoattractants by the intestinal epithelium. IP-10, Mig, and I-TAG are 3 CXC chemokines that are known to act as CD4(+) T-cell chemoattractants, Methods: We studied constitutive chemokine expression in human colon, and defined the regulated expression of these chemokines by reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistology using cultured human intestinal epithelial cell lines and a novel adaptation of an in vivo human intestinal xenograft model. Results: IP-10 and Mig were constitutively expressed by normal human colon epithelium, and their cognate receptor, CXCR3, was expressed by mucosal mononuclear cells. Interferon (IFN)-gamma stimulation increased mRNA expression and the polarized basolateral secretion of these chemokines by human colon epithelial cell lines; infection with enteroinvasive bacteria, or stimulation with the proinflammatory cytokines tumor necrosis factor or and interleukin la, strongly potentiated IFN-gamma -induced epithelial cell IP-10, Mig, and I-TAG production. Epithelial cell mRNA and protein expression of IP-10, Mig and I-TAG were rapidly up-regulated in human intestinal xenografts in response to stimulation with IFN-gamma alone or in combination with IL-1, Conclusions: The constitutive and regulated production of the IFN-gamma -inducible chemokines IP-10, Mig, and I-TAG by human intestinal epithelium, and the expression of their cognate receptor, CXCR3, by mucosal mononuclear cells, suggest that the intestinal epithelium can play a role in modulating physiologic and pathologic T cell-mediated mucosal inflammation.