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

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

Fingerprint Dive into the research topics of 'PlGF enhances TLR-dependent inflammatory responses in human mononuclear phagocytes'. Together they form a unique fingerprint.

Cite this