Cytotrophoblasts suppress macrophage-mediated inflammation through a contact-dependent mechanism.

Autor: Eastman AJ; Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Vrana EN; Vanderbilt University Medical School, Vanderbilt University, Nashville, TN, USA., Grimaldo MT; Texas A&M University, College of Agriculture and Life Sciences, College Station, TX, USA., Jones AD; Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Rogers LM; Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Alcendor DJ; Department of Medicine, Meharry Medical College, Nashville, TN, USA., Aronoff DM; Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
Jazyk: angličtina
Zdroj: American journal of reproductive immunology (New York, N.Y. : 1989) [Am J Reprod Immunol] 2021 Mar; Vol. 85 (3), pp. e13352. Date of Electronic Publication: 2020 Oct 16.
DOI: 10.1111/aji.13352
Abstrakt: Problem: 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 TNF-α production through secreted prostaglandin E 2 . We hypothesized that CTBs would also inhibit Mφ cytokine expression through secreted mediators.
Method of Study: THP.1 Mφ-like cells with an NF-κB 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. NF-κB was assessed via alkaline phosphatase assay, and proinflammatory mediators were assessed by qRT-PCR and ELISA.
Results: CTBs suppressed GBS- or TLR-stimulated Mφ NF-κB activity, and TNF-α 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.
Conclusions: CTBs limit Mφ NF-κB activation and production of TNF-α and MMP9 through an as-yet unknown, cell-to-cell contact-mediated mechanism. This suppression is distinct from the PGE 2 -mediated Mφ TNF-α suppression by DSC, suggesting that DSCs and CTBs regulate Mφ inflammation through distinct mechanisms. How Mφ integrates these signals in an intact GM will be paramount to determining causes and prevention of PPROM.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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