title: Serum neurotensin (NT) is increased in psoriasis and NT induces vascular endothelial growth factor release from human mast cells.
abstract: BACKGROUND
  Psoriasis involves skin inflammation that often worsens with stress, but the mechanism of this effect remains obscure. We have shown that corticotropin-releasing hormone (CRH) is increased in the serum of patients with psoriasis. A peptide, neurotensin (NT), can trigger skin histamine release and augment the ability of CRH to increase skin vascular permeability.
  
  
  OBJECTIVE
  To investigate the serum level of NT, and the expression of genes for NT and NT receptor-1 (NTR-1) in lesional and nonlesional skin of patients with psoriasis, compared with normal controls. Also, to study the effect of NT on human mast cell release of vascular endothelial growth factor (VEGF), which is increased in psoriatic skin.
  
  
  METHODS
  Serum was obtained from patients with psoriasis (n = 56) and controls (n = 33); NT levels were measured with the Milliplex microbead assay. Biopsies were obtained from the lesional and nonlesional skin of patients with chronic plaque psoriasis (n = 40), who had not received any treatment for at least 15 days and were free of any systemic inflammatory diseases. Control skin samples were obtained from healthy subjects (n = 30). Expression of genes for NT and NTR-1 in the skin was evaluated by quantitative reverse transcriptase-polymerase chain reaction. LAD2 human mast cells were stimulated by NT (1 μmol L(-1)) for 24 h and VEGF was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Serum NT was increased in patients with psoriasis, while expression of genes for NT and NTR-1 in lesional skin was decreased compared with controls. NT induced VEGF release from mast cells and was augmented by interleukin-33.
  
  
  CONCLUSIONS
  NT may play a role in psoriasis pathogenesis and its worsening by stress, at least in part through activation of skin mast cells.
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vasiadi
authors.forename: A
authors.initials: A
authors.lastname: Therianou
authors.forename: K D
authors.initials: KD
authors.lastname: Alysandratos
authors.forename: A
authors.initials: A
authors.lastname: Katsarou-Katsari
authors.forename: T
authors.initials: T
authors.lastname: Petrakopoulou
authors.forename: A
authors.initials: A
authors.lastname: Theoharides
authors.forename: E
authors.initials: E
authors.lastname: Papadavid
authors.forename: N
authors.initials: N
authors.lastname: Stavrianeas
authors.forename: C
authors.initials: C
authors.lastname: Antoniou
authors.forename: D
authors.initials: D
authors.lastname: Kalogeromitros
authors.forename: T C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008407:Mast Cells; D008875:Middle Aged; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000097:blood* / Q000235:genetics; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000150:complications; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018028:Receptors, Neurotensin; D042461:Vascular Endothelial Growth Factor A; C114036:neurotensin type 1 receptor; D009496:Neurotensin