Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environment at the ocular mucosal epithelium
Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environment at the ocular mucosal epithelium
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DOI：
10.4049/jimmunol.173.5.3337
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Kiyono, H
中科院分区：
文献类型：
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作者：
Ueta, M;Nochi, T;Kiyono, H
上皮细胞是粘膜免疫系统对抗入侵病原体的第一道防线的关键参与者。在本研究中，我们试图确定是否表达Toll样受体（TLR）的人角膜上皮细胞作为模式识别受体在先天免疫系统中的功能，如果是这样，这些TLR是否作为眼粘膜免疫的第一道防线。用肽聚糖或LPS孵育人原代角膜上皮细胞和人角膜上皮细胞系（HCE-T）不会导致NF-κ B在DNA转录水平的活化或炎症相关分子（如IL-6、IL-8和人β-防御素-2）的分泌。然而，当与IL-1 α孵育以激活NF-κ B时，这些细胞产生的炎症介质增强。观察到人角膜上皮细胞在细胞内表达TLR 2和TLR 4特异性mRNA及其相应的蛋白质，但不在细胞表面。然而，即使将LPS人工引入细胞质中，也不会导致上皮细胞的活化。两者合计，我们的结果表明，TLR 2和TLR 4在人角膜上皮细胞的细胞内表达未能引起先天性免疫应答，因此，可能是故意的，有助于眼粘膜上皮的免疫沉默环境。
Epithelial cells are key players in the first line of defense offered by the mucosal immune system against invading pathogens. In the present study we sought to determine whether human corneal epithelial cells expressing Toll-like receptors (TLRs) function as pattern-recognition receptors in the innate immune system and, if so, whether these TLRs act as a first line of defense in ocular mucosal immunity. Incubation of human primary corneal epithelial cells and the human corneal epithelial cell line (HCE-T) with peptidoglycan or LPS did not lead to activation, at the level of DNA transcription, of NF-kappaB or the secretion of inflammation-associated molecules such as IL-6, IL-8, and human beta-defensin-2. However, when incubated with IL-1alpha to activate NF-kappaB, the production by these cells of such inflammatory mediators was enhanced. Human corneal epithelial cells were observed to express both TLR2- and TLR4-specific mRNA as well as their corresponding proteins intracellularly, but not at the cell surface. However, even when LPS was artificially introduced into the cytoplasm, it did not lead to the activation of epithelial cells. Taken together, our results demonstrate that the intracellular expression of TLR2 and TLR4 in human corneal epithelial cells fails to elicit innate immune responses and therefore, perhaps purposely, contributes to an immunosilent environment at the ocular mucosal epithelium.