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Transforming growth factor-β1 promotes nasal mucosal mast cell chemotaxis in murine experimental allergic rhinitis
Yuhui Ouyang1, Atsuhito Nakao, Demin Han
1Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing Institute of Otolaryngology, Beijing, China.
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.
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