Cytotrophoblasts suppress macrophage-mediated inflammation through a contact-dependent mechanism.
Am J Reprod Immunol
; 85(3): e13352, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-32969101
ABSTRACT
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 E2 . 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 PGE2 -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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estreptocócicas
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Streptococcus
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Ruptura Prematura de Membranas Fetais
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Células Estromais
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Decídua
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Âmnio
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Inflamação
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Macrófagos
Limite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Am J Reprod Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos