title: Corticotropin releasing hormone and Urocortin 2 activate inflammatory pathways in cultured trophoblast cell lines.
abstract: OBJECTIVE
  Embryo implantation and parturition are recognized as inflammatory events involving endocrine and immune system. NF-kB and MAPK are two transcription factor families involved in inflammation. A possible role of neuroendocrine mechanism in early pregnancy and delivery was proposed for the neuropeptides related to corticotropin releasing hormones (CRH), named Urocortins (Ucns). Experimental and clinical studies support a role for CRH, Ucn, Ucn2 and Ucn3 in the endocrine/immune modulation of inflammation in human trophoblast; however the intracellular mechanisms are not yet recognized. The aim of the present study was to evaluate which of these neuropeptides modulate NF-kB or MAPKs pathways.
  
  
  METHODS
  In Jeg-3 placental cell line the effect of CRH, Ucn, Ucn2 or Ucn3 on NF-kB and MAPKs pathways were evaluated using Western blot analysis.
  
  
  RESULTS
  CRH induced the phosphorylation of MAPK subunits; Ucn2 was able to induce the phosphorylation of both NF-kB and MAPK subunits. Ucn and Ucn3 had no effects on these pathways.
  
  
  CONCLUSIONS
  These data provide novel information on inflammatory process in trophoblast cells: Ucn2 is a potent pro-inflammatory neuropeptide via NF-kB and MAPK pathways and CRH via MAPK, and CRH and Ucn2 network participates in the inflammatory mechanisms of pregnancy and parturition.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena Viale Bracci, Siena, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Novembri
authors.affiliation: Department of Biotechnology, University of Siena, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: De Clemente
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena Viale Bracci, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Funghi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena Viale Bracci, Siena, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Torricelli
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena Viale Bracci, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Voltolini
authors.affiliation: The University of Western Australia M460A, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Challis
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena Viale Bracci, Siena, Italy. Electronic address: felice.petraglia@unisi.it.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D054832:Urocortins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D006728:Hormones; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; C576814:UCN protein, human; C426705:UCN2 protein, human; C426704:UCN3 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CRH; Jeg 3; MAPK; NF-kB; Urocortin 2