Bax is crucial for IFN-gamma-induced resolution of allergen-induced mucus cell metaplasia.
Allergic airway responses cause proliferation of epithelial cells and mucus cell metaplasia ( MCM), and the resolution of MCM involves reduction of cell numbers. The role of inflammation and apoptosis on this process was investigated in P-selectin +/+ and -/- mice sensitized and challenged with OVA by analyzing the expression and the role of regulators of apoptosis in metaplastic mucus cells. No differences were observed in MCM at 5 days of allergen exposure between +/+ and -/- mice, despite reduced IL-13 levels in -/- mice. Although IL-4 levels were similar in both -/- and +/+ mice, IL-13 and IL-5 levels had decreased and IFN-gamma levels were increased earlier in -/- compared with +/+ mice. MCM levels were decreased 4-fold at 7 days of allergen exposure in -/- mice and at 15 days in +/+ mice. The percentage of Bax-expressing mucus cells increased significantly at 7 days in -/- mice and at 10 days in +/+ mice. The Bax-positive mucus cells exhibited caspase-specific cleavage of cytokeratin 18. IFN-gamma caused Bax expression in IL-13- induced MCM in microdissected airway cultures. MCM remained significantly elevated in Bax -/- mice following 15 days of allergen exposure compared with +/+ mice, while the number of eosinophils was reduced in both Bax +/+ and -/- mice at 15 days. Together, these data demonstrate that reduced IL-13 levels were sufficient to elicit maximum MCM, that IFN-gamma induces Bax in metaplastic mucus cells, and that Bax plays a critical role in the resolution of MCM, but not in the resolution of eosinophils.[1]References
- Bax is crucial for IFN-gamma-induced resolution of allergen-induced mucus cell metaplasia. Tesfaigzi, Y., Fischer, M.J., Daheshia, M., Green, F.H., De Sanctis, G.T., Wilder, J.A. J. Immunol. (2002) [Pubmed]
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