title: Epigen is induced during the interleukin-13-stimulated cell proliferation in murine primary airway epithelial cells.
abstract: 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.
authors.affiliation: Department of Pediatrics, Saga University, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Aoki
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D066261:Epigen; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D018793:Interleukin-13 / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D011799:Quinazolines; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: C587855:Epgn protein, mouse; D066261:Epigen; D018793:Interleukin-13; D008024:Ligands; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D066246:ErbB Receptors