title: Urocortin increases IL-4 and IL-10 secretion and reverses LPS-induced TNF-alpha release from human trophoblast primary cells.
abstract: OBJECTIVE
  As urocortin (Ucn) is a placental peptide belonging to the corticotrophin-releasing hormone (CRH) family that modulates immune function in other biological models, this study evaluated Ucn effects on cytokines secretion from cultured human trophoblast cells.
  
  
  METHODS
  Placentas were collected from normal term pregnancies after elective caesarean section, and primary trophoblast culture was prepared followed by the treatment of Ucn and/or CRH selective antagonists, antalarmin and astressin 2b. The anti-inflammatory cytokines IL-4 and IL-10 and the pro-inflammatory cytokine TNF-alpha were measured by ELISA.
  
  
  RESULTS
  Urocortin treatment induced a significant and dose-dependent increase of IL-4 and IL-10, whereas it did not affect TNF-alpha secretion. When incubated in the presence of LPS, Ucn reversed LPS-induced TNF-alpha release from cultured trophoblast cells, an effect that was blocked by the CRH-R2 selective antagonist, astressin 2b.
  
  
  CONCLUSIONS
  Urocortin stimulates IL-4 and IL-10 secretion and reverses LPS-induced TNF-alpha release from trophoblast cells through action on CRH-R2 receptors, suggesting that this peptide may play a possible role as an anti-inflammatory agent.
authors.affiliation: Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Torricelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Voltolini
authors.forename: Enrrico
authors.initials: E
authors.lastname: Bloise
authors.forename: Giulia
authors.initials: G
authors.lastname: Biliotti
authors.forename: Alessia
authors.initials: A
authors.lastname: Giovannelli
authors.forename: Maria
authors.initials: M
authors.lastname: De Bonis
authors.forename: Alberto
authors.initials: A
authors.lastname: Imperatore
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011247:Pregnancy; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054832:Urocortins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D014409:Tumor Necrosis Factor-alpha; D054832:Urocortins; C528574:astressin-2B; D016753:Interleukin-10; D015847:Interleukin-4