人子宫内膜上皮细胞中Toll样受体(TLR)的表达及TLR介导的细胞因子/趋化因子产生
Toll-like receptor (TLR) expression and TLR-mediated cytokine/chemokine production by human uterine epithelial cells.
作者信息
Schaefer Todd M, Desouza Kristin, Fahey John V, Beagley Kenneth W, Wira Charles R
机构信息
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
出版信息
Immunology. 2004 Jul;112(3):428-36. doi: 10.1111/j.1365-2567.2004.01898.x.
The objective of this study was to examine the expression of toll-like receptors (TLRs) by the uterine epithelial cell line ECC-1 and to determine if stimulation of the expressed TLRs induces changes in cytokine and/or chemokine secretion. The expression of TLR1 to TLR9 by ECC-1 cells was demonstrated by reverse transcription polymerase chain reaction, with only TLR10 not being expressed. Stimulation of ECC-1 cells using agonists to TLR2, TLR4 and TLR5 induced the expression of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1), as well as the pro-inflammatory cytokine IL-6, and occurred in a dose-dependent manner. In response to zymosan and flagellin, pathogen-associated molecular patterns (PAMP) that are recognized by TLR2 and TLR5 respectively, ECC-1 cells secreted significantly more IL-8, MCP-1 and IL-6 than in response to other TLR agonists. In contrast, agonists to TLR3, TLR7, and TLR9 had no effect on the secretion of the 13 cytokines or chemokines analysed. These results indicate that uterine epithelial cells are important sentinels of the innate immune system. Further it indicates that all but one of the known TLRs are expressed by ECC-1 cells and that stimulation through specific TLRs mediates changes in the expression of key chemokines and pro-inflammatory cytokines that aid in the defence of the uterus against potential pathogens.
本研究的目的是检测子宫上皮细胞系ECC-1中Toll样受体(TLRs)的表达,并确定所表达的TLRs的刺激是否会诱导细胞因子和/或趋化因子分泌的变化。通过逆转录聚合酶链反应证实了ECC-1细胞中TLR1至TLR9的表达,只有TLR10未表达。使用TLR2、TLR4和TLR5的激动剂刺激ECC-1细胞可诱导趋化因子白细胞介素-8(IL-8)和单核细胞趋化蛋白-1(MCP-1)以及促炎细胞因子IL-6的表达,且呈剂量依赖性。分别对zymosan和鞭毛蛋白(分别由TLR2和TLR5识别的病原体相关分子模式)作出反应时,ECC-1细胞分泌的IL-8、MCP-1和IL-6明显多于对其他TLR激动剂的反应。相比之下,TLR3、TLR7和TLR9的激动剂对所分析的13种细胞因子或趋化因子的分泌没有影响。这些结果表明子宫上皮细胞是先天性免疫系统的重要前哨。此外,这表明除一种已知TLR外,其他所有TLR均由ECC-1细胞表达,并且通过特定TLR的刺激介导关键趋化因子和促炎细胞因子表达的变化,有助于子宫抵御潜在病原体。