The AMPK-TSC1/2-mTOR signaling pathway regulates cigarette smoking-induced inflammation and apoptosis in airway epithelial cells

Background: Cigarette smoking (CS)-induced inflammation and apoptosis are critical for the development of chronic obstructive pulmonary disease (COPD). Methods: Human bronchial epithelial cells(HBECs) were silenced by small interfering (si) RNAs for TSC2, mTOR , Raptor and Rictor , and were then treated with CS. Expression of mTOR signaling related molecules (p-AMPK, TSC2, p-TSC2, mTOR, p-mTOR, p-S6),Inflammatory cytokines interleukin (IL)-6 and IL-8,cleaved caspase-9 and -3 and autophagy were detected by RT-PCR, ELISA,western blotting,Annexin V/PI staining or immunocytochemistry. Results: CSE induced notable activation of AMPKα and Tsc1/2 while markedly down-regulated mTOR in HBECs.Besides, mTOR activity, as revealed by levels of p-S6, was dramatically decreased in CS-exposed mouse airways or COPD lung tissues. Knockout of TSC2 significantly protected against CSE-induced inflammation and apoptosis, whereas silencing mTOR expression with siRNA or starvation exerted converse effects. Conclusion: mTOR signaling pathway plays an important role in CS–induced airway inflammation and apoptosis, eventually participating in COPD.