title: Neuropeptide substance P induces mRNA expression and secretion of CXCL8 chemokine, and HDC in human umbilical cord blood mast cells.
abstract: OBJECTIVE
  Mast cells play an important role in innate and acquired immunity and are thought to be the cellular origin of most proteases and cytokines. Substance P (SP) and its receptor, NK-1R, play critical roles in immune regulation in human and animal models of inflammation.
  
  
  METHODS
  We used mature human cord blood mast cells (HCBMC) differentiated from cord blood CD34+ precursor activated with SP in culture.
  
  
  RESULTS
  Our data indicate that Substance P strongly activates mature HCBMC in releasing CXCL8 expression and secretion (
  
  
  METHODS
  1.200 +/- 1.0; SP: 4.10 +/- 0.90; P < 0.01). Moreover, in a RT-PCR, HCBMC expressed CXCL8 mRNA after Substance P activation. Since calcium ionophore A23187 is a pharmacological activator that raises cytosolic free calcium ion concentraion and stimulates mast cells in the production and secretion of proinflammatory compounds, it was used as positive control. In addition, we found that HCBMCs generate the transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, after SP treatment. Since CXCL8 is a member of the CXC chemokine subfamily with potent chemotactic activity and is a primary inflammatory cytokine we conclude that our results, obtained from HCBMC cultures, a good and valid model in vitro, support the concept that the neurogenic system modulates inflammatory events by Substance P-mediated HCBMC chemokine CXCL8 release.
  
  
  CONCLUSIONS
  The expression, synthesis and release of CXCL8 suggest an increase of inflammatory process in vivo mediated by the recruitment and infiltration of inflammatory cells in inflamed tissues.
authors.affiliation: Immunology Division, Medical School, University ofChieti-Pescara, Italy. mlcastellani@unich.it
authors.forename: M L
authors.initials: ML
authors.lastname: Castellani
authors.forename: C
authors.initials: C
authors.lastname: Ciampoli
authors.forename: M
authors.initials: M
authors.lastname: Felaco
authors.forename: S
authors.initials: S
authors.lastname: Tetè
authors.forename: C M
authors.initials: CM
authors.lastname: Conti
authors.forename: V
authors.initials: V
authors.lastname: Salini
authors.forename: D
authors.initials: D
authors.lastname: De Amicis
authors.forename: C
authors.initials: C
authors.lastname: Orso
authors.forename: P L
authors.initials: PL
authors.lastname: Antinolfi
authors.forename: A
authors.initials: A
authors.lastname: Caraffa
authors.forename: G
authors.initials: G
authors.lastname: Cerulli
authors.forename: P
authors.initials: P
authors.lastname: Boscolo
authors.forename: T C
authors.initials: TC
authors.lastname: Theoharides
authors.forename: P
authors.initials: P
authors.lastname: Conti
authors.forename: D
authors.initials: D
authors.lastname: Kepuraj
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D006640:Histidine Decarboxylase / Q000235:genetics*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000494:pharmacology*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D012333:RNA, Messenger; D013373:Substance P; D000001:Calcimycin; D003907:Dexamethasone; D006640:Histidine Decarboxylase