title: Effects of Cytokines and TLR Ligands on the Production of PlGF and sVEGFR1 in Primary Trophoblasts.
abstract: OBJECTIVE
  Cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) play an important role in maintaining pregnancy. Toll-like receptors (TLRs) have also been associated with innate immune responses during pregnancy. Placenta growth factor (PlGF) is one of the angiogenic factors and soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is one of the antiangiogenic factors that regulate PlGF function. To elucidate the effects of cytokines and TLR ligands on the production of angiogenic and antiangiogenic factors in trophoblasts, we examined the production of PlGF and sVEGFR1 from trophoblasts following stimulation with cytokines and TLR ligands.
  
  
  METHODS
  Villous tissues were obtained from healthy pregnant women who had had an artificial abortion. The trophoblasts were isolated from villous tissues. Subsequently, trophoblasts were treated with TNF-α, IFN-γ and TLR ligands. The levels of PlGF and sVEGFR1 were measured by enzyme-linked immunosorbent assay. The expression of those mRNA was analyzed using quantitative reverse transcription PCR.
  
  
  RESULTS
  The production of PlGF in trophoblasts increased by the addition of TNF-α or IFN-γ and decreased by TLR4 ligand. sVEGFR1 levels also increased by following the stimulation with IFN-γ or TLR ligand.
  
  
  CONCLUSIONS
  Cytokines such as TNF-α and IFN-γ and TLR ligands may contribute to the production of angiogenic and antiangiogenic factors and may affect the placental formation.
authors.affiliation: Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Kato
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Fumihisa
authors.initials: F
authors.lastname: Chishima
mesh_terms: D043924:Angiogenesis Modulating Agents / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008024:Ligands; D000072483:Placenta Growth Factor / Q000096:biosynthesis*; D011247:Pregnancy; D051193:Toll-Like Receptors / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
chemical_list: D043924:Angiogenesis Modulating Agents; D016207:Cytokines; D008024:Ligands; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000072483:Placenta Growth Factor; D007371:Interferon-gamma; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1