Article
TGF-β1 promotes nasal mucosal mast cell chemotaxis in mouse models of allergic rhinitis
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Published: | April 4, 2012 |
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Background: Recent studies have shown that transforming growth factor-beta 1 (TGF-β1) plays an important role in the progression of allergic diseases. To explore the effect of TGF-β1 on mast cells in the progression and regulation of allergic rhinitis, the expression of TGF-β1 in the nasal mucosa in mouse models of allergic rhinitis was analyzed.
Methods: Mouse models of allergic rhinitis were established by ovalbumin (OVA) sensitization and challenge; immunostaining was used to analyze the expression of TGF-β1 in the mouse nasal mucosa; a chemotaxis assay was conducted to analyze the impact of TGF-β1 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-β1 stimulation.
Results: It was found that TGF-β1 expression was induced in allergic rhinitis and that pSmad2 was expressed in mast cells present in the nasal mucosa. TGF-β1 could induce migration of mast cells, but HTS466284, a TGF-β receptor 1 kinase inhibitor, inhibited this chemotactic activity (P <0.05). Western blot analysis demonstrated that after TGF-β1 stimulation, mast cell RhoA expression was significantly increased (P <0.001). TGF-β1-induced mast cell chemotaxis could be inhibited by the RhoA inhibitor Tat-C3 and myosin light chain kinase (MLCK) inhibitor ML-7.
Conclusion: TGF-β1 plays a major role in inducing the accumulation of mast cells in allergic rhinitis. Inhibition of TGF-β1 signaling activation might be a potential new target for the prevention and treatment of allergic rhinitis.