Nod1 Activation by Bacterial iE-DAP Induces Maternal-Fetal Inflammation and Preterm Labor
Nod1 Activation by Bacterial iE-DAP Induces Maternal-Fetal Inflammation and Preterm Labor
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DOI：
10.4049/jimmunol.1100578
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发表时间：
2011-07-15
影响因子：
4.4
通讯作者：
Abrahams, Vikki M.
中科院分区：
文献类型：
--
作者：
Cardenas, Ingrid;Mulla, Melissa J.;Abrahams, Vikki M.
感染与早产之间有很强的联系；然而，潜在的机制在很大程度上仍然未知。Nod1和Nod2是细胞内模式识别受体，可被细菌肽激活并介导先天免疫。我们之前证明了人类妊娠早期滋养细胞表达Nod1和Nod2，它们在刺激时引发炎症。本研究旨在确定Nod1和Nod2在妊娠晚期滋养细胞中的表达和功能，并表征Nod1激活对妊娠结局的体内影响。人足月胎盘组织和离体足月滋养细胞表达Nod1，但不表达Nod2。在滋养细胞培养中，Nod1的激动剂细菌γ -d -谷氨酰胺-中二氨基戊酸（iE-DAP）激活诱导了促炎细胞因子谱，与对照组相比，其特征是分泌的IL-6、gro - α和MCP-1水平升高。然而，这些细胞因子在细菌MDP刺激Nod2时并没有上调。在胚胎第14.5天给妊娠的C57BL/6J小鼠高剂量的细菌iE-DAP可在24 h内诱发早产，但较低剂量的iE-DAP不会导致早产，但会降低胎儿体重，改变母胎界面的细胞因子谱，并诱导胎儿炎症。因此，功能性Nod1在整个妊娠期间由滋养细胞表达，并可能在介导感染相关炎症和早产中发挥作用。这项研究表明，模式识别受体，而不是tlr，可能涉及或参与感染相关的早产。免疫学杂志，2011,18(7):980-986。
There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-alpha, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal-fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor. The Journal of Immunology, 2011, 187: 980-986.