title: Gefitinib, an EGFR Tyrosine Kinase inhibitor, Prevents Smoke-Mediated Ciliated Airway Epithelial Cell Loss and Promotes Their Recovery.
abstract: Cigarette smoke exposure is a major health hazard. Ciliated cells in the epithelium of the airway play a critical role in protection against the noxious effects of inhaled cigarette smoke. Ciliated cell numbers are reduced in smokers which weakens host defense and leads to disease. The mechanisms for the loss of ciliated cells are not well understood. The effects of whole cigarette smoke exposure on human airway ciliated ciliated cells were examined using in vitro cultures of normal human bronchial epithelial cells and a Vitrocell® VC 10® Smoking Robot. These experiments showed that whole cigarette smoke causes the loss of differentiated ciliated cells and inhibits differentiation of ciliated cells from undifferentiated basal cells. Furthermore, treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, Gefitinib, during smoke exposure prevents ciliated cell loss and promotes ciliated cell differentiation from basal cells. Finally, restoration of ciliated cells was inhibited after smoke exposure was ceased but was enhanced by Gefitinib treatment. These data suggest that inhibition of EGFR activity may provide therapeutic benefit for treating smoke related diseases.
authors.affiliation: Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Valencia-Gattas
authors.affiliation: Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Conner
authors.affiliation: Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Nevis L
authors.initials: NL
authors.lastname: Fregien
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*
chemical_list: C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012906:Smoke; D066246:ErbB Receptors; D000077156:Gefitinib