Levocetirizine inhibits rhinovirus-induced up-regulation of fibrogenic and angiogenic factors in nasal polyp fibroblasts

Am J Rhinol Allergy. 2011 Nov-Dec;25(6):416-20. doi: 10.2500/ajra.2011.25.3684.

Abstract

Background: Up-regulation of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta, may contribute to the formation of nasal polyps (NPs). Rhinovirus (RV) infection enhances expression of MMP-2, MMP-9, and VEGF in NP fibroblasts and of TGF-beta in respiratory epithelial cells. We investigated the inhibitory effects of levocetirizine (LCT) on the RV-induced expression of (1) fibrogenic (MMPs and TGF-beta) and (2) angiogenic (VEGF and TGF-beta) factors in NP fibroblasts.

Methods: NP fibroblasts obtained from 11 male patients with chronic rhinosinusitis with NPs (CRSwNPs), were infected with RV serotype 16 (RV-16) for 4 hours. Cells were treated with 50 nM of LCT 24 hours before infection and for 48 hours thereafter. Expression of MMP-2, MMP-9, VEGF, and TGF-β mRNA and protein were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively.

Results: LCT significantly inhibited RV-induced increases in MMP-2, MMP-9, VEGF, and TGF-beta mRNA, and protein expression, in NP fibroblasts (p < 0.05 for each comparison).

Conclusion: LCT inhibits RV-induced up-regulation of fibrogenic and angiogenic factors in NP fibroblasts, suggesting that LCT may prevent NP formation in patients with CRSwNP caused by RV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cetirizine / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / virology
  • Fibrosis
  • Gene Expression Regulation, Viral / drug effects
  • Histamine H1 Antagonists, Non-Sedating / pharmacology*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Nasal Polyps / drug therapy*
  • Nasal Polyps / physiopathology
  • Nasal Polyps / virology
  • Neovascularization, Pathologic / metabolism
  • Picornaviridae Infections / drug therapy*
  • Picornaviridae Infections / physiopathology
  • Picornaviridae Infections / virology
  • Rhinovirus / pathogenicity
  • Rhinovirus / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult

Substances

  • Histamine H1 Antagonists, Non-Sedating
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • levocetirizine
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Cetirizine