Transforming growth factor-β1 promotes nasal mucosal mast cell chemotaxis in murine experimental allergic rhinitis

ORL J Otorhinolaryngol Relat Spec. 2012;74(3):117-23. doi: 10.1159/000328587. Epub 2012 Mar 17.

Abstract

Background: Recent studies have shown that transforming growth factor-β(1) (TGF-β(1)) plays an important role in the progression of allergic diseases.

Methods: Mouse models of allergic rhinitis were established by ovalbumin sensitization and challenge. Immunostaining was used to analyze the expression of TGF-β(1) in the mouse nasal mucosa. A chemotaxis assay was conducted to analyze the impact of TGF-β(1) stimulation on migration of mast cells differentiated from mouse bone marrow cells. Chemotaxis and Western blot analysis were further applied to investigate the pathways involved in mast cell migration induced by TGF-β(1) stimulation.

Results: TGF-β(1) expression was induced in allergic rhinitis and phosphorylated Smad2 was expressed in mast cells present in the nasal mucosa. TGF-β(1) could induce migration of mast cells, but HTS466284, a TGF-β receptor 1 kinase inhibitor, inhibited this chemotactic activity. After TGF-β(1) stimulation, mast cell RhoA expression was significantly increased. TGF-β(1)-induced mast cell chemotaxis could be inhibited by the RhoA inhibitor Tat-C3 and myosin light chain kinase inhibitor ML-7.

Conclusion: TGF-β(1) plays a major role in inducing the accumulation of mast cells in allergic rhinitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / pharmacology
  • Animals
  • Azepines / pharmacology
  • Botulinum Toxins / pharmacology
  • Chemotaxis / drug effects
  • Chemotaxis / immunology*
  • Disease Models, Animal
  • Disease Progression
  • Enzyme Inhibitors / pharmacology
  • Female
  • Mast Cells / cytology*
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Naphthalenes / pharmacology
  • Nasal Mucosa / cytology
  • Nasal Mucosa / immunology*
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Rhinitis, Allergic, Perennial / immunology*
  • Smad2 Protein / metabolism
  • Specific Pathogen-Free Organisms
  • Transforming Growth Factor beta1 / immunology*
  • rhoA GTP-Binding Protein / antagonists & inhibitors
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Azepines
  • Enzyme Inhibitors
  • Naphthalenes
  • Smad2 Protein
  • Smad2 protein, mouse
  • Transforming Growth Factor beta1
  • ML 7
  • Ovalbumin
  • ADP Ribose Transferases
  • exoenzyme C3, Clostridium botulinum
  • Botulinum Toxins
  • rhoA GTP-Binding Protein