PlGF enhances TLR‐dependent inflammatory responses in human mononuclear phagocytes. (20th June 2017)

• Record Type: Journal Article
• Authors: Newell, Laura F.; Holtan, Shernan G.; Yates, Jane E.; Pereira, Leonardo; Tyner, Jeffrey W.; Burd, Irina; Bagby, Grover C.
• Is Part Of: American journal of reproductive immunology. Volume 78:Number 4(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06-20
• Subjects: innate immunity -- mononuclear phagocytes -- placental growth factor -- pregnancy -- toll‐like receptors -- viral infections; Human reproduction -- Immunological aspects -- Periodicals; 616.69206
• DOI: 10.1111/aji.12709
• Languages: English
• ISSNs: 1046-7408

Abstract

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.