title: Histamine induces human lung fibroblast-mediated collagen gel contraction via histamine H1 receptor.
abstract: BACKGROUND
  Airway remodeling is implicated in irreversible airflow limitation of refractory asthma, which includes increased smooth muscle mass and subepithelial fibrosis. Activated fibroblasts acquire contractile phenotype to participate in tissue contraction and structural alteration of extracellular matrices. Histamine is a potent mediator of allergic inflammation, substantially involved in asthmatic pathophysiology.
  
  
  OBJECTIVE
  We hypothesized that histamine might play a role in airway remodeling, and investigated its effect on fibroblast-mediated collagen gel contraction.
  
  
  METHODS
  Fibroblast-mediated collagen gel contraction was studied. Histamine's regulation of collagen gel contraction was characterized by using specific histamine-receptor antagonists, an IP3 receptor antagonist and a PKC inhibitor.
  
  
  RESULTS
  Histamine induced contraction of collagen gels embedded with human lung fibroblasts, in a time-dependent manner, and at the concentration more than 10(-6) M, both in four primary cultured adult lung fibroblasts and three fetal lung fibroblast cell lines. This effect was attenuated by H1 receptor antagonist, whereas those for H2 to H4 receptors failed to show an inhibitory effect. Furthermore, IP3 receptor-mediated Ca(2+) mobilization was implicated in histamine's action on collagen gel contraction.
  
  
  CONCLUSIONS
  Our results suggest that histamine is involved in airway remodeling through its action on lung fibroblasts, and antihistamine drugs, especially H1 receptor antagonists, might be potentially beneficial for a subset of asthmatic patients.
authors.affiliation: 1Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Horie
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Yu
authors.initials: Y
authors.lastname: Mikami
authors.forename: Makiko
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Taisuke
authors.initials: T
authors.lastname: Jo
authors.forename: Jun
authors.initials: J
authors.lastname: Nakajima
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D011969:Receptors, Histamine H1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011969:Receptors, Histamine H1; D006632:Histamine; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D002118:Calcium