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Pl GF enhances TLR ‐dependent inflammatory responses in human mononuclear phagocytes
Author(s) -
Newell Laura F.,
Holtan Shernan G.,
Yates Jane E.,
Pereira Leonardo,
Tyner Jeffrey W.,
Burd Irina,
Bagby Grover C.
Publication year - 2017
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12709
Subject(s) - chemokine , peripheral blood mononuclear cell , inflammation , proinflammatory cytokine , immunology , tumor necrosis factor alpha , phosphorylation , toll like receptor , receptor , biology , chemistry , microbiology and biotechnology , immune system , innate immune system , biochemistry , in vitro
Problem Levels of placental growth factor (Pl GF ) peak during third trimester of pregnancy, a time when women are at increased risk of virus‐induced morbidity. We hypothesized Pl GF might contribute to an exaggerated inflammatory response to Toll‐like receptor ( TLR ) activation. Method of study Primary human adult and cord blood CD 14 + cells were cultured in the presence of TLR ligands and/or Pl GF . Results Pl GF 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 Pl GF / TLR effect involved multiple inflammatory cytokines/chemokines and was seen with the majority of TLR agonists. Pl GF enhanced phosphorylation of IkappaB kinase ( IKK ) in monocytes stimulated with the TLR ‐7/8 agonist R848, and IKK inhibition completely suppressed the Pl GF effect. Conclusion Pl GF 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.