PlGF enhances TLR-dependent inflammatory responses in human mononuclear phagocytes

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

Research output: Contribution to journalArticle

4 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)
JournalAmerican Journal of Reproductive Immunology
DOIs
StateAccepted/In press - 2017

Keywords

  • Innate immunity
  • Mononuclear phagocytes
  • Placental growth factor
  • Pregnancy
  • Toll-like receptors
  • Viral infections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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