Activation of toll-like receptors 2 or 3 and preterm delivery in the mouse

Activation of toll-like receptors 2 or 3 and preterm delivery in the mouse
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DOI:
10.1177/1933719107302959
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发表时间:
2007-05-01
影响因子:
2.9
通讯作者:
Hirsch, Emmet
Hirsch, Emmet
中科院分区:
医学4区
文献类型:
--
作者:
Ilievski, Vladimir;Lu, Shi-Jiang;Hirsch, Emmet

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本研究的目的是测试Toll样受体(TLR)2和3(分别为革兰氏阳性和病毒病原体的先天免疫受体)的激活是否可以诱导早产。在妊娠约75%时,对早产CD-1小鼠的一个子宫角注射TLP-2配体(脂磷壁酸[LTA]或肽聚糖[PGN])或TLR-3配体聚肌苷酸:胞苷酸(poly [I:C])。记录早产。在另一组小鼠中,用PGN或poly(I:C)处理后5小时,通过逆转录酶聚合酶链反应定量组织mRNA。宫内PGN和LTA诱导早产,在最大剂量下达到100%。腹膜内PGN也诱导早产,但发生率较低(最高= 55%)。子宫内聚(1:Q)诱导早产的小鼠高达31%。Poly(I:C)诱导子宫干扰素β和趋化因子(C-C基序)配体5(CCL5,也称为RANTES),但不诱导白细胞介素10、肿瘤坏死因子或脂多糖诱导的CXC趋化因子。与生理盐水相比,PGN没有改变这些mRNA。两种处理均未诱导胎膜中的基因表达。TLR-2或TLR-3的活化可诱导小鼠中的早产。TLR-3与poly(I:C)的激活在子宫组织中诱导干扰素β和趋化因子CCL5,但在胎膜中不诱导。
The objective of this study is to test whether the activation of toll-likc receptors (TLRs) 2 and 3 (innate immune receptors for gram-positive and viral pathogens, respectively) can induce preterm delivery. One uterine horn of preterm pregnant CD-1 mice at approximately 75% of gestation was injected with TLP-2 ligands (lipoteichoic acid [LTA] or peptidoglycan [PGN]) or the TLR-3 ligand polyinosinic:cytidylic acid (poly[I:C]). Preterm delivery was recorded. In a separate group of mice, tissue mRNAs were quantified by reverse transcriptase polymerase chain reaction 5 hours after treatment with PGN or poly(I:C). Intrauterine PGN and LTA induced preterm delivery, reaching 100% at maximal doses. Intraperitoneal PGN also induced preterm delivery but at lower rates (maximum = 55%). Intrauterine poly(1:Q induced preterm birth in up to 31% of mice. Poly(I:C) induced uterine interferon beta and chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) but not interleukin 10, tumor necrosis factor, or lipopolysaccharide-induced CXC chemokine. PGN did not alter these mRNAs when compared with saline. Neither treatment induced gene expression in fetal membranes. Activation of either TLR-2 or -3 can induce preterm delivery in the mouse. Activation of TLR-3 with poly(I:C) induces interferon beta and the chemokine CCL5 in uterine tissues but not in fetal membranes.