Regulation of apoptosis and innate immune stimuli in inflammation-induced preterm labor.
Regulation of apoptosis and innate immune stimuli in inflammation-induced preterm labor.
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DOI：
10.4049/jimmunol.1301604
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发表时间：
2013-12-01
期刊：
影响因子：
--
通讯作者：
Beaman KD
中科院分区：
文献类型：
--
作者：
Jaiswal MK;Agrawal V;Mallers T;Gilman-Sachs A;Hirsch E;Beaman KD
先天免疫反应是成功着床和胎盘形成所必需的。这部分受V-ATP酶α 2亚型（α 2 V）以及M1（炎症）和M2（抗炎）巨噬细胞同时浸润子宫和胎盘的调节。本研究的目的是鉴定α 2 V在炎症诱导的小鼠早产中的作用及其与细胞凋亡和先天免疫应答的调节的关系。使用感染诱导的早产的小鼠模型，在妊娠第14.5天子宫内接种生理盐水或肽聚糖（PGN，一种toll样受体（TLR）2激动剂）和聚肌苷酸：胞苷酸（poly（I：C），一种TLR 3激动剂）后8小时收集妊娠组织，分别模拟革兰氏阳性细菌和病毒感染。在PGN+poly（I：C）诱导的早产过程中，胎盘、子宫和胎膜中a2 V的表达显著降低。PGN+poly（I：C）处理组胎盘和子宫组织中iNOS表达明显上调。PGN+poly（I：C）处理扰乱了粘附连接蛋白，并通过子宫蜕膜细胞和海绵滋养层细胞凋亡的外源性途径增加了凋亡细胞死亡。在PGN+poly（I：C）处理的子宫中，F4/80+巨噬细胞增加，并且极化偏向双阳性CD 11 c+（M1）和CD 206+（M2）细胞，这对于死亡细胞的清除和炎症的快速消退至关重要。PGN+poly（I：C）处理的子宫中Nlrp 3的表达和caspase-1的活化增加，可引起子宫的热凋亡。这些结果表明，PGN+poly（I：C）的双重打击通过减少a2 V表达并同时激活凋亡和炎症过程来诱导早产。
An innate immune response is required for successful implantation and placentation. This is regulated in part by a2 isoform of V-ATPase (a2V) and the concurrent infiltration of M1 (inflammatory) and M2 (anti-inflammatory) macrophages to the uterus and placenta. The objective of present study was to identify the role of a2V during inflammation-induced preterm labor in mice and its relationship to the regulation of apoptosis and innate immune responses. Using a mouse model of infection-induced preterm delivery, gestational tissues were collected 8 hrs after intrauterine inoculation on day 14.5 of pregnancy with either saline or peptidoglycan (PGN, a toll-like receptor (TLR) 2 agonist) and polyinosinic:cytidylic acid (poly(I:C), a TLR3 agonist), modeling Gram positive bacterial and viral infections, respectively. Expression of a2V decreased significantly in the placenta, uterus, and fetal membranes during PGN+poly(I:C) induced preterm labor. Expression of iNOS was significantly upregulated in PGN+poly(I:C) treated placenta and uterus. PGN+poly(I:C) treatment disturbed adherens junction proteins and increased apoptotic cell death via extrinsic pathway of apoptosis among uterine decidual cells and spongiotrophoblast. F4/80+ macrophages were increased and polarization was skewed in PGN+poly(I:C) treated uterus toward double positive CD11c+ (M1) and CD206+ (M2) cells, which are critical for the clearance of dying cells and rapid resolution of inflammation. Expression of Nlrp3 and activation of caspase-1 was increased in PGN+poly(I:C) treated uterus which could induce pyroptosis. These results suggest that double hit of PGN+poly(I:C) induces preterm labor via reduction of a2V expression and simultaneous activation of apoptosis and inflammatory processes.
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DOI：
10.1124/jpet.106.109280
发表时间：
2006-11-01
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
3.8
作者：
Jaiswal, Mukesh K.;Mallers, Timothy M.;Beaman, Kenneth D.
通讯作者：
Beaman, Kenneth D.
影响因子：
1.8
作者：
Esplin, MS;Romero, R;Adashi, EY
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