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 language | English (US) |
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Article number | e12709 |
Journal | American Journal of Reproductive Immunology |
Volume | 78 |
Issue number | 4 |
DOIs | |
State | Published - 2017 |
Bibliographical note
Publisher Copyright:© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Keywords
- innate immunity
- mononuclear phagocytes
- placental growth factor
- pregnancy
- toll-like receptors
- viral infections