title: Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts.
abstract: OBJECTIVE
  What are the effects of fatty acids on placental inflammatory cytokine with respect to toll-like receptor-4/nuclear factor-kappa B (TLR4/NF-kB)?
  
  
  CONCLUSIONS
  Exogenous fatty acids induce a pro-inflammatory cytokine response in human placental cells in vitro via activation of TLR4 signaling pathways.
  
  
  BACKGROUND
  The placenta is exposed to changes in circulating maternal fatty acid concentrations throughout pregnancy. Fatty acids are master regulators of innate immune pathways through recruitment of toll-like receptors and activation of cytokine synthesis.
  
  
  METHODS
  Trophoblast cells isolated from 14 normal term human placentas were incubated with long chain fatty acids (FA) of different carbon length and degree of saturation. The expression and secretion of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Antibodies against TLR4 ligand binding domain, downstream signaling and anti-p65 NFkB-inhibitor were used to characterize the pathways of FA action.
  
  
  METHODS
  General approach used primary human term trophoblast cell culture. Methods and end-points used real-time quantitative PCR, cytokine measurements, immunohistochemistry, western blots.
  
  
  RESULTS
  The long chain saturated fatty acids, stearic and palmitic (PA), stimulated the synthesis as well as the release of TNF-α, IL-6 and IL-8 by trophoblast cells (2- to 6-fold, P < 0.001). In contrast, the unsaturated (palmitoleic, oleic, linoleic) acids did not modify cytokine expression significantly. Palmitate-induced inflammatory effects were mediated via TLR4 activation, NF-kB phosphorylation and nuclear translocation.
  
  
  CONCLUSIONS
  TNF-α protein level was close to the limit of detection in the culture medium even when cells were cultured with PA.
  
  
  CONCLUSIONS
  These mechanisms open the way to a better understanding of how changes in maternal lipid homeostasis may regulate placental inflammatory status.
  
  
  BACKGROUND
  X.Y. was recipient of fellowship award from West China Second University Hospital, Sichuan University (NIH HD 22965-19). The authors have nothing else to disclose.
  
  
  BACKGROUND
  None.
authors.affiliation: Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109-1998, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yang
authors.affiliation: Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109-1998, USA.
authors.forename: Maricela
authors.initials: M
authors.lastname: Haghiac
authors.affiliation: Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109-1998, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Glazebrook
authors.affiliation: Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109-1998, USA.
authors.forename: Judi
authors.initials: J
authors.lastname: Minium
authors.affiliation: Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109-1998, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Catalano
authors.affiliation: Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109-1998, USA shdemouzon@metrohealth.org.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hauguel-de Mouzon
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; D005227:Fatty Acids; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C495345:TLR4 protein, human; C439524:TNF protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: NF-kB; cytokine; fatty acids; human; inflammation; placenta; toll-like receptor 4; trophoblasts