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 Vitrocell1 VC 101 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.
| Original language | English (US) |
|---|---|
| Article number | e0160216 |
| Journal | PLoS One |
| Volume | 11 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2016 |
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ASJC Scopus subject areas
- Medicine(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Gefitinib, an EGFR tyrosine kinase inhibitor, prevents smoke-mediated ciliated airway epithelial cell loss and promotes their recovery. / Valencia-Gattas, Monica; Conner, Gregory E; Fregien, Nevis L.
In: PLoS One, Vol. 11, No. 8, e0160216, 01.08.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gefitinib, an EGFR tyrosine kinase inhibitor, prevents smoke-mediated ciliated airway epithelial cell loss and promotes their recovery
AU - Valencia-Gattas, Monica
AU - Conner, Gregory E
AU - Fregien, Nevis L.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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 Vitrocell1 VC 101 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.
AB - 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 Vitrocell1 VC 101 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.
UR - http://www.scopus.com/inward/record.url?scp=84984783715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84984783715&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0160216
DO - 10.1371/journal.pone.0160216
M3 - Article
C2 - 27532261
AN - SCOPUS:84984783715
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0160216
ER -