| First Author | Wyatt TA | Year | 2012 |
| Journal | Am J Pathol | Volume | 181 |
| Issue | 2 | Pages | 431-40 |
| PubMed ID | 22677421 | Mgi Jnum | J:187004 |
| Mgi Id | MGI:5435112 | Doi | 10.1016/j.ajpath.2012.04.022 |
| Citation | Wyatt TA, et al. (2012) Co-exposure to cigarette smoke and alcohol decreases airway epithelial cell cilia beating in a protein kinase cepsilon-dependent manner. Am J Pathol 181(2):431-40 |
| abstractText | Alcohol use disorders are associated with increased lung infections and exacerbations of chronic lung diseases. Whereas the effects of cigarette smoke are well recognized, the interplay of smoke and alcohol in modulating lung diseases is not clear. Because innate lung defense is mechanically maintained by airway cilia action and protein kinase C (PKC)-activating agents slow ciliary beat frequency (CBF), we hypothesized that the combination of smoke and alcohol would decrease CBF in a PKC-dependent manner. Primary ciliated bronchial epithelial cells were exposed to 5% cigarette smoke extract plus100 mmol/L ethanol for up to 24 hours and assayed for CBF and PKCepsilon. Smoke and alcohol co-exposure activated PKCepsilon by 1 hour and decreased both CBF and total number of beating cilia by 6 hours. A specific activator of PKCepsilon, DCP-LA, slowed CBF after maximal PKCepsilon activation. Interestingly, activation of PKCepsilon by smoke and alcohol was only observed in ciliated cells, not basal bronchial epithelium. In precision-cut mouse lung slices treated with smoke and alcohol, PKCepsilon activation preceded CBF slowing. Correspondingly, increased PKCepsilon activity and cilia slowing were only observed in mice co-exposed to smoke and alcohol, regardless of the sequence of the combination exposure. No decreases in CBF were observed in PKCepsilon knockout mice co-exposed to smoke and alcohol. These data identify PKCepsilon as a key regulator of cilia slowing in response to combined smoke and alcohol-induced lung injury. |
