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Mucosal-Immunity of gastrointestinal tract : immunological interactions of gastrointestinal epithelium

胃肠道粘膜免疫：胃肠道上皮的免疫相互作用

基本信息

批准号：
13670805
负责人：
ODA Megumi
金额：
$ 2.62万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670805/
关键词：
immune organ gastrointestinal tract mucosal immunity chemokine mast cell in vitro model of GI tract

项目摘要

1.Neutrophil-mesenchymal interactions and the regulation of intestinal epithelial ion secretion. In this model of the intestinal mucosa, intestinal myofibroblasts and subepithelial PMNs release products that directly stimulate intestinal epithelial cells to secrete Cl. In adition,18CO cells appear to enhance PMN-mediated alterations of epithelial secretion. The pro-inflammatory cytokine, IL-1,further augments 18CO-mediated epithelial secretion by inflammatory secretagogues including those released from PMNs. These data suggest that immune-mesenchymal interactions are important in the regulation of intestinal epithelial ion transport.2.We have compared constitutive and stimulated expression of IL-8,MIP-1α,MCP-1,and RANTES in human GI epithelial cell lines following stimulation with PMA and following exposure to S.typhimurium, poliovirus, and respiratory syncytial virus (RSV). IL-8 mRNA and protein was detected in all cell lines tested under basal conditions and both were stimulated by PMA and Salmonella infection. Constitutive and PMA- or Salmonella-stimulated MCP-1 and MIP-1α,were detected by PCR in T84 and Caco-2 but not HT-29 or KATO III. RANTES was expressed in 3 of 4 lines as measured by PCR but protein levels measured in cell supernates were low (except T84). We were unable to detect any effect of Salmonella on the induction of immunoreactive RANTES or MIP-1α. Inoculation of T84 with either poliovirus or RSV increased immunoreactive IL-8,RANTES and MIP-1α. These results suggest that gastrointestinal epithelial cells express a broad range of chemokines which are differentially regulated by bacteria and viruses.

1.中性粒细胞-间充质相互作用和肠上皮细胞离子分泌的调节。在这个模型的肠粘膜，肠肌成纤维细胞和上皮下中性粒细胞释放的产品，直接刺激肠上皮细胞分泌氯。此外，18 CO细胞似乎增强了PMN介导的上皮分泌的改变。促炎细胞因子IL-1通过炎性促分泌素（包括从PMN释放的促分泌素）进一步增强18 CO介导的上皮分泌。这些数据表明，免疫-间充质相互作用在肠上皮离子转运的调节中是重要的。2.我们比较了PMA刺激和暴露于鼠伤寒沙门氏菌、脊髓灰质炎病毒和呼吸道合胞病毒（RSV）后，人GI上皮细胞系中IL-8、MIP-1α、MCP-1和RANTES的组成型和刺激型表达。在基础条件下检测的所有细胞系中均检测到IL-8 mRNA和蛋白，并且均受到PMA和沙门氏菌感染的刺激。通过PCR在T84和Caco-2中检测到组成型和PMA或沙门氏菌刺激的MCP-1和MIP-1α，但在HT-29或KATO III中未检测到。通过PCR测量，4个细胞系中的3个细胞系表达RANTES，但细胞上清中测量的蛋白水平较低（T84除外）。我们无法检测沙门氏菌对免疫反应性RANTES或MIP-1α诱导的任何影响。T84细胞接种脊髓灰质炎病毒或呼吸道合胞病毒后，IL-8、RANTES和MIP-1α的免疫反应性均增加。这些结果表明，胃肠上皮细胞表达广泛的趋化因子，这些趋化因子受细菌和病毒的差异调节。