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Research on the innate immune system of the cornea

角膜先天免疫系统的研究

基本信息

批准号：
14571674
负责人：
KUMAGAI Naoki
金额：
$ 2.24万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571674/
关键词：
corneal fibroblasts LPS IL-8 MCP-1 ICAM-1 TLR-4 CD14 LBP

项目摘要

In order to clarify the roles of corneal cells in innate immune system of the cornea, we revealed the following facts1) Cultured human corneal fibroblasts express toll-like receptor (TLR)-4 and cluster of differentiation (CD) 14, which are the components of LPS receptors. These cells also express MD-2 protein, which is necessary for the proper distribution of LPS receptors on the cell membrane2) LPS derived from E Coli, P.aerubginosa and S Minnesota enhanced the expression of IL-8, MCP-1 and ICAM-1 by cultured human corneal fibroblast. This effect was time and dose-dependent. The effect of LPS on the expression on these proteins are E.coli> S.Minnesota>> P.aeruglnosa3) Human tear fluids did contain LBP and sCD14. The concentrations of these LPS-related proteins were about 1 micro gram 1 ml and 400 nano gram /ml, respectively. The concentrations of these LPS-related proteins were lower in the tear fluids than that in the serum measured with a same settings. There were no relationships b … More etween the concentration of these LPS-related proteins in the tear fluids and the serum4) Addition of LBP or sCD14 induced a dose dependent increase of IL-8 release and ICAM-1 expression by cultured human corneal fibroblasts. The stimulatory effect of these LPS-related proteins axe more pronounced at a concentration of the serum than that of the tear fluids5) Injection of LPS into a rabbit corneal stroma induced a corneal ulcer and corneal opacity. These corneal lesions are transient the cornea is healed spontaneously leaving corneal scarring. Histologically, infiltration of neutrophils is observed in to the corneal stromaOur study shows that the cells of the cornea, especially the corneal fibroblasts, play a role in the innate immune system of the outer eye. These cells perceive the presence of LPS, which is a common structure of Gram negative bacterial cell walls, and express neutrophils activation and chemotactic factors such as ICAM-1 and IL-8LPS-related proteins such as LBP or sCD14 enhance the perception of LPS by corneal cells Less

为了阐明角膜细胞在角膜固有免疫系统中的作用，我们揭示了以下事实：1)培养的人角膜成纤维细胞表达Toll样受体(TLR)-4和分化簇(CD)14，这是内毒素受体的组成部分。这些细胞也表达MD-2蛋白，这是内毒素受体在细胞膜上的正确分布所必需的。2)来自E-Coli、铜绿假单胞菌和明尼苏达S的内毒素促进培养的人角膜成纤维细胞表达IL-8、MCP-1和ICAM-1。这种效应具有时间和剂量依赖性。内毒素对这些蛋白表达的影响依次为：E.Coli&gt；S.Minneota&gt；&gt；P.Aeruglnosa3)人的泪液中确实含有LBP和sCD14。这些内毒素相关蛋白的浓度分别为1微克/毫升和400毫微克/毫升。在相同的环境下，泪液中这些内毒素相关蛋白的浓度低于血清中的浓度。没有和…的关系4)加入LBP或sCD14后，培养的人角膜成纤维细胞IL-8释放和ICAM-1表达呈剂量依赖性增加。在一定浓度的血清中，这些内毒素相关蛋白的刺激作用比泪液更明显。5)将内毒素注入兔角膜基质，引起角膜溃疡和角膜混浊。这些角膜损伤是暂时的，角膜会自动愈合，留下角膜疤痕。组织学上，可以观察到中性粒细胞在角膜基质中的渗透我们的研究表明，角膜的细胞，特别是角膜成纤维细胞，在外眼的先天免疫系统中发挥作用。这些细胞感知内毒素的存在，这是革兰氏阴性细菌细胞壁的常见结构，并表达中性粒细胞激活和趋化因子，如ICAM-1和IL-8。