Expression of toll-like receptors (TLR) and responsiveness to TLR agonists by polarized mouse uterine epithelial cells in culture
Expression of toll-like receptors (TLR) and responsiveness to TLR agonists by polarized mouse uterine epithelial cells in culture
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DOI：
10.1095/biolreprod.106.050690
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Wira, Charles R.
中科院分区：
文献类型：
--
作者：
Soboll, Gisela;Shen, Li;Wira, Charles R.
本研究的目的是检查小鼠子宫上皮细胞的Toll样受体（TLR）的表达，并确定表达的TLR的刺激是否诱导细胞因子和/或趋化因子分泌的变化。RT-PCR结果显示，小鼠子宫上皮细胞表达TLRs 1 - 6，TLRs 7 - 9仅周期性表达。在缺乏病原体相关分子模式的情况下，极化的子宫上皮细胞在体外组成性分泌白细胞介素（IL）1A、半胱氨酸-半胱氨酸配体（CCL）2、IL 6、粒细胞-巨噬细胞集落刺激因子2（CSF 2）、肿瘤坏死因子A（TNFA）、CSF 3和IL 8，分泌到顶端隔室中的细胞因子/趋化因子的水平显著高于释放到基底外侧隔室中的水平。当在分析前将TLR 2激动剂Pam（3）Cys-Ser-（Lys）（4）和TLR 1/6激动剂肽聚糖添加到顶端表面48 h时，与对照相比，增加了上皮细胞顶端分泌IL 1A、CCL 2和IL 6以及顶端/基底侧双向分泌CSF 2、TNFA、CSF 3和IL 8。TLR3-激动剂poly 0：0显著增加了CCL2、116、TNFA和CSF 2的双向分泌以及CSF 3的基底外侧分泌。最后，TLR4-激动剂脂多糖增加了CCL2、CSF 2、TNFA、CSF 3和IL 8的双向分泌以及IL 6的顶端分泌。这些结果表明，TIr1至TIr6的mRNA由子宫上皮细胞表达，并且用特异性TLR激动剂治疗改变了有助于子宫防御潜在病原体的关键趋化因子和促炎细胞因子的表达。
The objective of the present study was to examine the expression of Toll-like receptors (TLRs) by mouse uterine epithelial cells and to determine if stimulation of the expressed TLR induces changes in cytokine and/or chemokine secretion. Using RT-PCR, the expression of TLRs 1-6 by mouse uterine epithelial cells was demonstrated, with TLRs 7-9 expressed only periodically. In the absence of pathogen-associated molecular patterns, polarized uterine epithelial cells constitutively secrete interleukin (IL) 1A, cysteine-cysteine ligand (CCL) 2, IL6, granulocyte-macrophage colony-stimulating factor 2 (CSF2), tumor necrosis factor A (TNFA), CSF3, and IL8 in vitro, with levels of cytokines/chemokines secreted into the apical compartment being significantly greater than those released into the basolateral compartment. When added to the apical surface for 48 h before analysis, the TLR2-agonist Pam(3)Cys-Ser-(Lys)(4) and TLR1/6-agonist peptidoglycan increased epithelial cell apical secretion of IL1A, CCL2, and IL6 and apical/basolateral bidirectional secretion of CSF2, TNFA, CSF3, and IL8 when compared to controls. The TLR3-agonist poly 0:0 significantly increased bidirectional secretion of CCL2, 116, TNFA, and CSF2 and basolateral secretion of CSF3. Lastly, the TLR4-agonist lipopolysaccharide increased bidirectional secretion CCL2, CSF2, TNFA, CSF3, and IL8 and apical secretion of IL6. These results indicate that mRNAs for TIr1 through TIr6 are expressed by uterine epithelial cells and that treatment with specific TLR agonists alters the expression of key chemokines and proinflammatory cytokines that contribute to the defense of the uterus against potential pathogens.