Gefitinib Prevents Bleomycin-induced Lung Fibrosis in Mice

• DOI: 10.1164/rccm.200509-1534oc
• Publication Date: 2006-06-02T01:01:53Z
• Authors: Yoshiki Ishii; Sakae Fujimoto; Takeshi Fukuda
• Keywords: EGFR Inhibitors

Transforming growth factor-alpha and epidermal factor (EGF), the ligands for EGF receptor (EGFR), stimulate fibroblast proliferation play an important role in pathogenesis of pulmonary fibrosis. Therefore, inhibition EGFR signal by tyrosine kinase inhibitor (EGFR-TKI) may prevent However, there is a possibility that blocking inhibit epithelial cell repair, thereby exaggerating lung fibrosis.To investigate effect EGFR-TK on fibrosis.We looked at effects EGFR-TKIs gefitinib (20, 90, 200 mg/kg) AG1478 (12 bleomycin-induced fibrosis model mice.Gefitinib prevented all three doses. Furthermore, those mice did not receive bleomycin treatment, mg/kg induce Immunohistochemistry revealed phosphorylation mesenchymal cells induced was inhibited gefitinib. also attenuated In vitro studies further demonstrated addition or suppressed ligand-induced fibroblasts.These findings suggest that, preclinical setting, have protective bleomycin. Because these molecular targeted drugs differing depending species individuals, cautious interpretation warranted.