title: Placental Regulation of Inflammation and Hypoxia after TNF-α Infusion in Mice.
abstract: OBJECTIVE
  Increased levels of inflammatory cytokines are demonstrated in the serum of women with pre-eclampsia. TNF-α infusion in animal models induces proteinuric hypertension similar to human pre-eclampsia. The effect of TNF-α on regulation of the immune and hypoxic pathways in the developing placenta and their relationship with experimental pre-eclampsia remains unexamined.
  
  
  METHODS
  TNF-α was infused into pregnant mice, and the effects on maternal hypertension, proteinuria, circulating levels of sFlt-1 and corresponding placental changes in molecules responding to inflammation (TLR-3 and TLR-4) and hypoxia (HIF-1α) were examined.
  
  
  RESULTS
  TNF-α infusion resulted in maternal hypertension and proteinuria. Molecular changes in the placenta involved upregulation of TLR-3, TLR-4 and HIF-1α. Serum levels of sFlt-1 were high in pregnant animals, but not further upregulated by TNF-α infusion.
  
  
  CONCLUSIONS
  A role for maladaptive regulation of TLR and HIF-1α induced by an imbalance in inflammatory cytokines is implicated in the pathogenesis of pre-eclampsia.
authors.affiliation: School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bobek
authors.affiliation: School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Surmon
authors.affiliation: Department of Physiology, Monash University, Melbourne, Vic, Australia.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Mirabito
authors.affiliation: School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.|The Heart Research Institute, University of Sydney, Sydney, NSW, Australia.|Liverpool Hospital, Renal Unit Liverpool, Liverpool, NSW, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Makris
authors.affiliation: School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.|The Heart Research Institute, University of Sydney, Sydney, NSW, Australia.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Hennessy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Cytokines; HIF-1; mouse; placenta; pre-eclampsia; toll-like receptor