Co-exposure to cigarette smoke and alcohol decreases airway epithelial cell cilia beating in a protein kinase Cε-dependent manner.

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 agents slow ciliary beat frequency (CBF), we hypothesized that the combination of smoke and alcohol would decrease CBF in a 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 Smoke and alcohol co-exposure activated by 1 hour and decreased both CBF and total number of beating cilia by 6 hours. A specific activator of DCP-LA, slowed CBF after maximal duanyu1531ε activation. Interestingly, activation of duanyu1531ε 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, duanyu1531ε activation preceded CBF slowing. Correspondingly, increased duanyu1531ε 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 duanyu1531ε knockout mice co-exposed to smoke and alcohol. These data identify duanyu1531ε as a key regulator of cilia slowing in response to combined smoke and alcohol-induced lung injury.

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