NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells.
NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells.
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人胎盘Hofbauer细胞NLRP3炎症体功能与嗜热性细胞死亡
DOI：
10.1016/j.jri.2020.103214
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发表时间：
2020-11
影响因子：
3.4
通讯作者：
Guller S
中科院分区：
文献类型：
--
作者：
Abrahams VM;Tang Z;Mor G;Guller S
霍夫鲍尔细胞（HBCs）数量和蛋白/基因表达的改变可能在微生物驱动/细胞因子介导的胎盘炎症中发挥作用，并在随后的妊娠并发症如绒毛炎、组织学绒毛膜羊膜炎和胎儿炎症反应综合征中发挥作用。焦亡是由炎性小体介导的一种炎症性细胞死亡形式，炎性小体是一种多蛋白复合物，它驱动白细胞介素1β (IL-1β)的加工和分泌。非胎盘巨噬细胞中的细菌脂多糖（LPS）和三磷酸腺苷（ATP）可通过激活NLRP3炎性体引发焦亡。然而，炎症体活化和焦亡在HBC病理生理中的作用尚不清楚。从人足月胎盘中分离的HBCs分别单独或联合LPS或ATP处理。用LPS和ATP处理HBCs可诱导高水平IL-1β的快速分泌，同时导致核凝聚和细胞肿胀相关的细胞死亡。用LPS和ATP处理HBC可诱导caspase-1激活、介导焦亡的gasdermin D （GSDMD）裂解和IL-1β加工。NLRP3下调后，Caspase-1激活、GSDMD切割、IL-1β加工和IL-1β分泌均显著减少；caspase-1的抑制；以及抑制介导K+外排的受体P2X7。综上所述，我们的数据表明，LPS和ATP处理刺激了HBCs中NLRP3炎性体的激活和焦亡，导致IL-1β的快速释放。由于HBC的定位赋予了影响微生物相关的胎盘和胎儿炎症的独特能力，这些研究表明炎症小体和焦亡在介导HBC驱动的炎症中起着关键作用。
Alterations in the number and protein/gene expression of Hofbauer cells (HBCs) may play a role in microbial-driven/cytokine-mediated placental inflammation, and in subsequent pregnancy complications such as villitis, histologic chorioamnionitis, and the fetal inflammatory response syndrome. Pyroptosis is an inflammatory form of cell death mediated by the inflammasome, a multi-protein complex which drives the processing and secretion of interleukin 1 beta (IL-1β). Pyroptosis can be triggered by bacterial lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in non-placental macrophages through activation of the NLRP3 inflammasome. However, the role of inflammasome activation and pyroptosis in HBC pathophysiology remains unclear. HBCs isolated from human term placentas were treated with or without LPS or ATP, alone or in combination. Treatment of HBCs with both LPS and ATP induced the rapid secretion of high levels of IL-1β and at the same time, cell death associated with nuclear condensation and cellular swelling. HBC treatment with both LPS and ATP induced caspase-1 activation, gasdermin D (GSDMD) cleavage, which mediates pyroptosis, and IL-1β processing. Caspase-1 activation, GSDMD cleavage, IL-1β processing, and IL-1β secretion were all significantly reduced following NLRP3 knockdown; inhibition of caspase-1; and inhibition of P2X7, the receptor that mediates K+ efflux. Together, our data indicate that LPS and ATP treatment stimulated NLRP3 inflammasome activation and pyroptosis in HBCs leading to the rapid release of IL-1β. Since the localization of HBCs confers a unique ability to influence microbial-associated placental and fetal inflammation, these studies suggest a key role for the inflammasome and pyroptosis in mediating HBC driven inflammation.
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DOI：
10.4049/jimmunol.1601179
发表时间：
2017-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brien ME;Duval C;Palacios J;Boufaied I;Hudon-Thibeault AA;Nadeau-Vallée M;Vaillancourt C;Sibley CP;Abrahams VM;Jones RL;Girard S
通讯作者：
Girard S
影响因子：
7.3
作者：
Reyes L;Golos TG
通讯作者：
Golos TG
形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
Kagan JC
DOI：
10.1111/j.1471-0528.2010.02728.x
发表时间：
2011-01
期刊：
BJOG : an international journal of obstetrics and gynaecology
影响因子：
--
作者：
Adams Waldorf KM;Rubens CE;Gravett MG
通讯作者：
Gravett MG
影响因子：
64.8
作者：
Shi, Jianjin;Zhao, Yue;Shao, Feng
通讯作者：
Shao, Feng