Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines
Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines
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DOI：
10.1016/j.molimm.2007.02.007
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发表时间：
2007-05-01
影响因子：
3.6
通讯作者：
Takada, Haruhiko
中科院分区：
文献类型：
--
作者：
Uehara, Akiko;Fujimoto, Yukari;Takada, Haruhiko
上皮细胞可以形成人体组织中抵抗细菌的第一道屏障。我们最近发现，口腔上皮细胞产生的抗菌因子，如肽聚糖识别蛋白（PGRP）和P-防御素2，但不是促炎细胞因子，如白细胞介素-8（IL-8），刺激后与细菌细胞表面成分。在本研究中，我们发现Toll样受体（TLR）2，TLR 3，TLR 4，TLR 7，NOD 1和NOD 2在口腔，舌，唾液腺，咽，食管，肠，宫颈，乳腺，肺和肾脏上皮细胞中有明确的表达。然而，舌、唾液腺、咽、食管、肠、宫颈、乳腺、肺和肾上皮细胞以及口腔上皮细胞不响应于化学合成的TLR和NOD激动剂模拟微生物组分而分泌IL-6、IL-8或单核细胞趋化蛋白-1：TLR 2激动性脂肽（Pam 3CSSNA）、TLR 3激动性聚LC、TLR 4激动性脂质A（LA-15-PP），TLR 7激动性单链RNA（ssPoly U）、NOD 1激动性iE-DAP（γ-D-铝氨酰-异硫代-二亚氨基庚二酸）和NOD 2激动性胞壁酰二肽（MDP）。尽管口腔上皮细胞上的PGRP在用这些合成组分刺激后显著上调，但咽上皮细胞上的PGRP仅略微上调，并且食管、肠和宫颈上皮细胞上的PGRP在用这些组分刺激后不上调。与此相反，刺激与合成的TLR和NODs配体诱导P-防御素2的产生在所有上皮细胞检查。这些发现表明，TLR和NOD在各种上皮细胞的功能受体，诱导抗菌反应一般不伴随炎症反应。(c)2007爱思唯尔有限公司版权所有。
Epithelial cells may form the first barrier of defense against bacteria in human tissues. We recently revealed that oral epithelial cells generated anti-bacterial factors, such as peptidoglycan recognition proteins (PGRPs) and P-defensin 2, but not proinflammatory cytokines, such as interleukin-8 (IL-8), upon stimulation with bacterial cell-surface components. In this study, we found clear expressions of Toll-like receptor (TLR)2, TLR3, TLR4, TLR7, NOD1 and NOD2 in oral, tongue, salivary gland, pharyngeal, esophageal, intestinal, cervical, breast, lung, and kidney epithelial cells. However, tongue, salivary gland, pharyngeal, esophageal, intestinal, cervical, breast, lung, and kidney epithelial cells, as well as oral epithelial cells, did not secrete IL-6, IL-8 or monocyte chemoattractant protein-1 in response to chemically synthesized TLR and NOD agonists mimicking microbial components: TLR2 agonistic lipopeptide (Pam3CSSNA), TLR3 agonistic Poly LC, TLR4 agonistic lipid A (LA-15-PP), TLR7 agonistic single stranded RNA (ssPoly U), NOD1 agonistic iE-DAP (gamma-D-alumtamyl-nieso-diafninopimelic acid), and NOD2 agonistic muramyldipeptide (MDP). Although PGRPs on oral epithelial cells were significantly up-regulated upon stimulation with these synthetic components, PGRPs on pharyngeal epithelial cells were only slightly up-regulated, and PGRPs on esophageal, intestinal and cervical epithelial cells were not up-regulated upon stimulation with the components. In contrast, stimulation with synthetic TLRs and NODs ligands induced P-defensin 2 generation in all epithelial cells examined. These findings indicate that TLR and NOD in various epithelial cells are functional receptors that induce anti-bacterial responses in general without being accompanied by inflammatory responses. (c) 2007 Elsevier Ltd. All rights reserved.