| First Author | Bailey KL | Year | 2018 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 315 |
| Issue | 5 | Pages | L882-L890 |
| PubMed ID | 30211654 | Mgi Jnum | J:271720 |
| Mgi Id | MGI:6280177 | Doi | 10.1152/ajplung.00033.2018 |
| Citation | Bailey KL, et al. (2018) Oxidative stress associated with aging activates protein kinase Cepsilon, leading to cilia slowing. Am J Physiol Lung Cell Mol Physiol 315(5):L882-L890 |
| abstractText | Older people are four times more likely to develop pneumonia than younger people. As we age, many components of pulmonary innate immunity are impaired, including slowing of mucociliary clearance. Ciliary beat frequency (CBF) is a major determinant of mucociliary clearance, and it slows as we age. We hypothesized that CBF is slowed in aging because of increased oxidative stress, which activates PKCepsilon signaling. We pharmacologically inhibited PKCepsilon in ex vivo mouse models of aging. We measured a slowing of CBF with aging that was reversed with inhibition using the novel PKC inhibitor, Ro-31-8220, as well as the PKCepsilon inhibitor, PKCe141. Inhibition of PKCepsilon using siRNA in mouse trachea also returned CBF to normal. In addition, antioxidants decrease PKCepsilon activity and speed cilia. We also aged wild-type and PKCepsilon KO mice and measured CBF. The PKCepsilon KO mice were spared from the CBF slowing of aging. Using human airway epithelial cells from younger and older donors at air-liquid interface (ALI), we inhibited PKCepsilon with siRNA. We measured a slowing of CBF with aging that was reversed with siRNA inhibition of PKCepsilon. In addition, we measured bead clearance speeds in human ALI, which demonstrated a decrease in bead velocity with aging and a return to baseline after inhibition of PKCepsilon. In summary, in human and mouse models, aging is associated with increased oxidant stress, which activates PKCepsilon and slows CBF. |
