Autophagy augmentation alleviates cigarette smoke-induced CFTR-dysfunction, ceramide-accumulation and COPD-emphysema pathogenesis

Abstract In this study, we aimed to investigate precise mechanism(s) of sphingolipid-imbalance and resulting ceramide-accumulation in COPD-emphysema. Where, human and murine emphysema lung tissues or human bronchial epithelial cells (Beas2b) were used for experimental analysis. We found that lungs of smokers and COPD-subjects with increasing emphysema severity demonstrate sphingolipid-imbalance, resulting in significant ceramide-accumulation and increased ceramide/sphingosine ratio, as compared to non-emphysema/non-smoker controls. Next, we found a substantial increase in emphysema chronicity-related ceramide-accumulation in murine (C57BL/6) lungs, while sphingosine levels only slightly increased. In accordance, the expression of the acid ceramidase decreased after CS-exposure. Moreover, CS-induced (sub-chronic) ceramide-accumulation was significantly (p