PlGF enhances TLR-dependent inflammatory responses in human mononuclear phagocytes

Laura F. Newell, Shernan G. Holtan, Jane E. Yates, Leonardo Pereira, Jeffrey W. Tyner, Irina Burd, Grover C. Bagby

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Problem: Levels of placental growth factor (PlGF) peak during third trimester of pregnancy, a time when women are at increased risk of virus-induced morbidity. We hypothesized PlGF might contribute to an exaggerated inflammatory response to Toll-like receptor (TLR) activation. Method of study: Primary human adult and cord blood CD14+ cells were cultured in the presence of TLR ligands and/or PlGF. Results: PlGF significantly enhanced the magnitude and duration of TNF messenger RNA and protein production by TLR-7/8-activated monocytes, and increased subsequent production of TNF-independent inflammatory cytokines. This PlGF/TLR effect involved multiple inflammatory cytokines/chemokines and was seen with the majority of TLR agonists. PlGF enhanced phosphorylation of IkappaB kinase (IKK) in monocytes stimulated with the TLR-7/8 agonist R848, and IKK inhibition completely suppressed the PlGF effect. Conclusion: PlGF enhances TLR-signaling upstream of IKK and contributes to an exaggerated pathologic pro-inflammatory state in response to activation of maternal and fetal mononuclear phagocytes by specific TLR agonists.

Original languageEnglish (US)
Article numbere12709
JournalAmerican Journal of Reproductive Immunology
Volume78
Issue number4
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
Office of Research on Women’s Health and the National Institute of Child Health and Human Development, Grant/Award Number: K12HD043488; Kuse Family Foundation Pilot Award.

Funding Information:
The authors would like to thank Katie Thoms, RN, Haley McClung, RN, Ashley Manning, PA, and Rogelyn Kwock, FNP, for their interest in our research and for their technical support. This work was supported in part by the Office of Research on Women’s Health and the National Institute of Child Health and Human Development, Oregon BIRCWH Award Number K12HD043488 (L.F.N. and S.G.H.), and the Kuse Family Foundation Pilot Award (L.F.N.).

Keywords

  • innate immunity
  • mononuclear phagocytes
  • placental growth factor
  • pregnancy
  • toll-like receptors
  • viral infections

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