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人输卵管上皮细胞对Toll样受体3激动剂聚肌苷酸-聚胞苷酸的抗病毒反应

Antiviral responses of human Fallopian tube epithelial cells to toll-like receptor 3 agonist poly(I:C).

作者信息

Ghosh Mimi, Schaefer Todd M, Fahey John V, Wright Jacqueline A, Wira Charles R

机构信息

Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.

出版信息

Fertil Steril. 2008 May;89(5 Suppl):1497-506. doi: 10.1016/j.fertnstert.2007.05.023. Epub 2007 Jul 31.

Abstract

OBJECTIVE

To examine the expression of toll-like receptors (TLR) by primary human Fallopian tube epithelial cells (FTEC) and to determine whether exposure to the TLR3 agonist poly(I:C) induces an antiviral response.

DESIGN

Tissue culture study.

SETTING

University medical center.

PATIENT(S): Premenopausal women undergoing hysterectomy.

INTERVENTION(S): Primary human FTEC were grown to confluence and high transepithelial resistance and treated with TLR agonists. Conditioned media was collected and RNA was extracted and analyzed for the expression of cytokines, chemokines, and antimicrobial genes.

MAIN OUTCOME MEASURE(S): The RNA was analyzed by real-time polymerase chain reaction and protein levels were assessed by enzyme-linked immunosorbent assay.

RESULT(S): The FTEC were demonstrated to express TLR1-9 but not 10. Treatment of FTEC with TLR3 agonist poly(I:C) resulted in increased expression of interleukin-8, tumor-necrosis factor alpha, human beta-defensin 2, interferon beta, and interferon stimulated genes myxovirus resistance gene 1, 2',5'-oligoadenylate synthetase, and protein kinase R. Additionally, FTEC exposed to poly(I:C) also resulted in the induction of TLR2, TLR3, and TLR7.

CONCLUSION(S): Our results suggest that FTEC are sensitive to viral infection and/or exposure to viral double-stranded RNA and can respond by secreting proinflammatory cytokines that mediate the initiation of an inflammatory response as well as expressing genes that can directly inhibit viral replication.

摘要

目的

检测原代人输卵管上皮细胞(FTEC)中Toll样受体(TLR)的表达,并确定暴露于TLR3激动剂聚肌苷酸胞嘧啶核苷酸(poly(I:C))是否会诱导抗病毒反应。

设计

组织培养研究。

单位

大学医学中心。

患者

接受子宫切除术的绝经前女性。

干预措施

将原代人FTEC培养至汇合状态并具有高跨上皮电阻,然后用TLR激动剂进行处理。收集条件培养基,提取RNA并分析细胞因子、趋化因子和抗菌基因的表达。

主要观察指标

通过实时聚合酶链反应分析RNA,通过酶联免疫吸附测定评估蛋白质水平。

结果

FTEC被证明表达TLR1 - 9,但不表达TLR10。用TLR3激动剂poly(I:C)处理FTEC导致白细胞介素-8、肿瘤坏死因子α、人β-防御素2、干扰素β以及干扰素刺激基因Mx1(抗黏液病毒基因1)、2',5'-寡腺苷酸合成酶和蛋白激酶R的表达增加。此外,暴露于poly(I:C)的FTEC还导致TLR2、TLR3和TLR7的诱导。

结论

我们的结果表明,FTEC对病毒感染和/或暴露于病毒双链RNA敏感,并且可以通过分泌介导炎症反应启动的促炎细胞因子以及表达可直接抑制病毒复制的基因来做出反应。

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