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Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus.

ABSTRACT: PROBLEM:During pregnancy, Group B Streptococcus (GBS) can infect fetal membranes to cause chorioamnionitis, resulting in adverse pregnancy outcomes. Macrophages are the primary resident phagocyte in extraplacental membranes. Protein kinase D (PKD) was recently implicated in mediating pro-inflammatory macrophage responses to GBS outside of the reproductive system. This work aimed to characterize the human placental macrophage inflammatory response to GBS and address the extent to which PKD mediates such effects. METHOD:Primary human placental macrophages were infected with GBS in the presence or absence of a specific, small molecule PKD inhibitor, CRT 0066101. Macrophage phenotypes were characterized by evaluating gene expression, cytokine release, assembly of the NLRP3 inflammasome, and NF?B activation. RESULTS:GBS evoked a strong inflammatory phenotype characterized by the release of inflammatory cytokines (TNF?, IL-1?, IL-6 (P ? 0.05), NLRP3 inflammasome assembly (P ? 0.0005), and NF?B activation (P ? 0.05). Pharmacological inhibition of PKD suppressed these responses, newly implicating a role for PKD in mediating immune responses of primary human placental macrophages to GBS. CONCLUSION:PKD plays a critical role in mediating placental macrophage inflammatory activation in response to GBS infection.

SUBMITTER: Sutton JA

PROVIDER: S-EPMC6459189 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus.

Sutton Jessica A JA Rogers Lisa M LM Dixon Beverly R E A BREA Kirk Leslie L Doster Ryan R Algood Holly M HM Gaddy Jennifer A JA Flaherty Rebecca R Manning Shannon D SD Aronoff David M DM

American journal of reproductive immunology (New York, N.Y. : 1989) 20190130 3

<h4>Problem</h4>During pregnancy, Group B Streptococcus (GBS) can infect fetal membranes to cause chorioamnionitis, resulting in adverse pregnancy outcomes. Macrophages are the primary resident phagocyte in extraplacental membranes. Protein kinase D (PKD) was recently implicated in mediating pro-inflammatory macrophage responses to GBS outside of the reproductive system. This work aimed to characterize the human placental macrophage inflammatory response to GBS and address the extent to which PK ...[more]

PMID: 30582878

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Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus.

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Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus.

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