title: The histamine-induced enhanced expression of vascular cell adhesion molecule-1 by nasal polyp-derived fibroblasts is inhibited by levocetirizine.
abstract: BACKGROUND
  Histamine, a key chemical mediator in allergic reaction, exhibits an array of pro-inflammatory effects that include the activation of fibroblasts. The aim of this study was to evaluate whether histamine could stimulate nasal polyp-derived fibroblasts to express vascular cell adhesion molecule (VCAM)-1, a surface molecule involved in structural-inflammatory cell interaction and whether levocetirizine could inhibit this induction.
  
  
  METHODS
  Primary nasal polyp tissue-derived fibroblasts were stimulated with histamine (10-1000 microM) or interleukin (IL)-4 plus tumor necrosis factor (TNF)-alpha (0.5-5 ng/mL) and VCAM-1 expression was evaluated by flow cytometry analysis. The inhibitory effect of the selective H1-antagonist levocetirizine (0.01-10.0 microM) on VCAM-1 expression was also tested.
  
  
  RESULTS
  Compared with unstimulated cultures, histamine or IL-4 + TNF-alpha, at the highest concentrations tested, significantly increase VCAM-1 expression (p < 0.05). To evaluate the ability of levocetirizine to downregulate VCAM-1 expression, fibroblasts were stimulated with histamine (1000 microM) or IL-4 + TNF-alpha (5 ng/mL), in the presence of the drug (0.01-10.0 microM). The histamine-induced VCAM-1 expression was effectively inhibited by levocetirizine (0.1-10.0 microM) (p < 0.05). No effect of the drug on IL-4 + TNF-alpha-induced VCAM-1 expression was observed.
  
  
  CONCLUSIONS
  Histamine upregulates VCAM-1 expression on nasal polyp-derived fibroblasts and this phenomenon, relevant to allergic late-phase inflammation, is effectively inhibited by levocetirizine.
authors.affiliation: Pulmonary Disease Unit, G. Gaslini Institute, Genoa, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Petecchia
authors.forename: Laura
authors.initials: L
authors.lastname: Serpero
authors.forename: Michela
authors.initials: M
authors.lastname: Silvestri
authors.forename: Federica
authors.initials: F
authors.lastname: Sabatini
authors.forename: Lucia
authors.initials: L
authors.lastname: Scarso
authors.forename: Giovanni A
authors.initials: GA
authors.lastname: Rossi
mesh_terms: D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017332:Cetirizine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D009298:Nasal Polyps / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D039563:Histamine H1 Antagonists, Non-Sedating; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4; C472067:levocetirizine; D006632:Histamine; D016650:Fluorescein-5-isothiocyanate; D017332:Cetirizine