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Publication
Protein kinase D mediates inflammatory responses of human placental macrophages
to Group B Streptococcus.
Authors Sutton JA, Rogers LM, Dixon B, Kirk L, Doster R, Algood HM, Gaddy JA, Flaherty
R, Manning SD, Aronoff DM
Submitted By Submitted Externally on 2/22/2019
Status Published
Journal American journal of reproductive immunology (New York, N.Y. : 1989)
Year 2018
Date Published 12/1/2018
Volume : Pages Not Specified : e13075
PubMed Reference 30582878
Abstract 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., 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., GBS evoked a strong inflammatory phenotype characterized by the
release of inflammatory cytokines (TNFa, IL-1ß, 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., PKD plays a critical role in mediating placental macrophage
inflammatory activation in response to GBS infection.




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