Cytotrophoblasts suppress macrophage-mediated inflammation through a contact-dependent mechanism.
Cytotrophoblasts suppress macrophage-mediated inflammation through a contact-dependent mechanism.
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DOI：
10.1111/aji.13352
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Aronoff DM
中科院分区：
文献类型：
--
作者：
Eastman AJ;Vrana EN;Grimaldo MT;Jones AD;Rogers LM;Alcendor DJ;Aronoff DM
胎膜（GM）感染引起炎症，可导致早产前胎膜破裂（PPROM）。GM的绒毛膜蜕膜层包括蜕膜基质细胞（DSC）、细胞滋养层细胞（CTB）和巨噬细胞（Mφ）。我们的实验室先前已经表明，DSCs通过分泌前列腺素E2抑制Mφ TNFα的产生。我们假设CTB也会通过分泌的介质抑制Mφ细胞因子的表达。将具有NFκB报告基因构建体的THP.1 Mφ样细胞或人血单核细胞衍生的Mφ与Jeg 3 CT B细胞系或原代人CTB共培养，并用B族链球菌（GBS）或Toll样受体（TLR）激动剂激发。在感染或处理前，将由CTB培养物产生的条件培养基应用于Mφ培养物。或者，将CTB与Mφ和GBS或TLR刺激的共孵育，但与Mφ和GBS或TLR刺激的物理分离。通过碱性磷酸酶测定法评估NFκB，通过qRT-PCR和ELISA评估促炎介质。CTBs抑制GBS或TLR刺激的Mφ NFκB活性、TNFα和MMP 9的产生。CTB和Mφ之间的直接物理接触是完全免疫抑制所必需的。增加Mφ/CTB的比值可克服免疫抑制。CTB通过一种未知的细胞间接触介导的机制限制了Mφ NFκB的活化和TNFα和MMP 9的产生。这种抑制作用与DSC对PGE 2介导的Mφ TNFα的抑制作用不同，表明DSC和CTB通过不同的机制调节Mφ炎症。Mφ如何将这些信号整合到完整的GM中，对于确定PPROM的病因和预防至关重要。
Gestational membrane (GM) infection provokes inflammation and can result in preterm prelabor rupture of membranes (PPROM). The choriodecidual layer of the GM includes decidual stromal cells (DSC), cytotrophoblasts (CTB) and macrophages (Mφ). Our laboratory has previously shown that DSCs suppress Mφ TNFα production through secreted prostaglandin E2. We hypothesized that CTBs would also inhibit Mφ cytokine expression through secreted mediators. THP.1 Mφ-like cells with an NFκB reporter construct or human blood monocyte-derived Mφ were co-cultured with the Jeg3 CTB cell line or primary human CTBs and challenged with Group B Streptococcus (GBS) or Toll-like receptor (TLR) agonists. Conditioned medium generated from CTB cultures was applied to Mφ cultures before infection or treatment. Alternatively, CTBs were co-incubated with, but physically separated from, Mφ and GBS or TLR-stimulated. NFκB was assessed via alkaline phosphatase assay and proinflammatory mediators were assessed by qRT-PCR and ELISA. CTBs suppressed GBS- or TLR-stimulated Mφ NFκB activity, TNFα and MMP9 production. Direct physical contact between CTBs and Mφ was required for full immunosuppression. Immunosuppression could be overcome by increasing the ratio of Mφ to CTB. CTBs limit Mφ NFκB activation and production of TNFα and MMP9 through an as-yet unknown, cell-to-cell contact-mediated mechanism. This suppression is distinct from the PGE2-mediated Mφ TNFα suppression by DSC, suggesting that DSCs and CTBs regulate Mφ inflammation through distinct mechanisms. How Mφ integrate these signals in an intact GM will be paramount to determining causes and prevention of PPROM.
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DOI：
10.4049/jimmunol.1700870
发表时间：
2017-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cross SN;Potter JA;Aldo P;Kwon JY;Pitruzzello M;Tong M;Guller S;Rothlin CV;Mor G;Abrahams VM
通讯作者：
Abrahams VM
影响因子：
2.4
作者：
Bae, Go-Eun;Honga, Joon-Seok;Roh, Cheong-Rae
通讯作者：
Roh, Cheong-Rae
影响因子：
3.8
作者：
Meinert, M.;Malmstroem, A.;Uldbjerg, N.
通讯作者：
Uldbjerg, N.
影响因子：
3.6
作者：
Hamelin-Morrissette, Jovane;Dallagi, Angham;Reyes-Moreno, Carlos
通讯作者：
Reyes-Moreno, Carlos
影响因子：
3.4
作者：
Bischof, P;Meisser, A;Campana, A
通讯作者：
Campana, A