title: Progesterone suppresses the fetal inflammatory response ex vivo.
abstract: OBJECTIVE
  Progesterone supplementation has been shown to be efficacious in preventing preterm birth. We sought to investigate the effects of progesterone on fetal inflammatory responses.
  
  
  METHODS
  Fetal mononuclear cells were isolated from umbilical cord blood and exposed to vehicle or progesterone (P4) for 1 hour prior to lipopolysaccharide (LPS) stimulation. Supernatants were assayed for tumor necrosis factor-alpha. Similar experiments were performed using cyclic adenosine monophosphate (cAMP) and progesterone modulators. The effect of P4 treatment on intracellular cAMP levels was also determined.
  
  
  RESULTS
  LPS treatment led to a significant increase in cytokine production by fetal mononuclear cells. Despite the lack of detectable nuclear progesterone receptors, P4 suppressed this inflammatory response. R5020 (progesterone agonist), forskolin (cAMP inducer), and dibutyryl cAMP (cAMP agonist) all achieved immunosuppression. The cAMP antagonist, Rp-cAMP, blocked the inhibitory effect of progesterone. P4 significantly increased intracellular cAMP levels.
  
  
  CONCLUSIONS
  Progesterone rapidly suppresses the fetal inflammatory response, possibly via nongenomic activation of the cAMP cascade.
authors: Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
authors: Nadav
authors: N
authors: Schwartz
authors: Xiangying
authors: X
authors: Xue
authors: Michal A
authors: MA
authors: Elovitz
authors: Oonagh
authors: O
authors: Dowling
authors: Christine N
authors: CN
authors: Metz
mesh_terms: D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005333:Fetus / Q000166:cytology / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000196:embryology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D000242:Cyclic AMP