Airway remodeling in
bronchial asthma is characterized by epithelial detachment and proliferation, subepithelial
fibrosis, increased smooth muscle mass, and goblet cell
hyperplasia. These features are mediated by T-helper type 2 (Th2)
cytokines including
interleukin (IL)-13. However, the direct effects of
IL-13 on the functions of airway epithelial cells are not fully understood. Murine primary airway epithelial (MPAE) cells were cultured in an air-liquid interface (ALI) culture system.
AG1478, a specific inhibitor of
epidermal growth factor receptor (EGFR)
tyrosine kinase, was used to examine whether EGFR was involved in the IL-13-stimulated proliferation of MPAE cells. The expressions of EGFR
ligands were investigated by
reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical analyses. The cell counting in cross-sections and [(3)H]
thymidine incorporation assays revealed a significant increase in the number of MPAE cells cultured with
IL-13 compared with a
phosphate-buffered saline (PBS) control.
AG1478 abolished the IL-13-stimulated proliferation of MPAE cells. The expression of
epigen, one of the EGFR
ligands, was enhanced in MPAE cells cultured with
IL-13. The findings suggest that EGFR is involved in the IL-13-stimulated proliferation of MPAE cells, and that
epigen is important for the proliferation process in
airway remodeling.