The histamine-induced enhanced expression of vascular cell adhesion molecule-1 by nasal polyp-derived fibroblasts is inhibited by levocetirizine

Am J Rhinol. 2006 Sep-Oct;20(5):445-9. doi: 10.2500/ajr.2006.20.0796.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cetirizine / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Gene Expression Regulation / drug effects
  • Histamine / pharmacology*
  • Histamine H1 Antagonists, Non-Sedating / pharmacology*
  • Humans
  • Immunophenotyping
  • Interleukin-4 / pharmacology
  • Male
  • Nasal Polyps / pathology*
  • Piperazines / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Fluorescent Dyes
  • Histamine H1 Antagonists, Non-Sedating
  • Piperazines
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Interleukin-4
  • levocetirizine
  • Histamine
  • Fluorescein-5-isothiocyanate
  • Cetirizine