Epigen is induced during the interleukin-13-stimulated cell proliferation in murine primary airway epithelial cells.
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.