标题：
MTOR suppresses autophagy-mediated airway epithelial injury in asthmatic inflammation
讲者：
吴银芳
单位：
浙江大学附属第二医院
播放：
681
论文摘要：
Rationale: Airway epithelial injury is known to influence the initiation and perpetuation of asthmatic inflammation, yet the detailed injury mechanisms remain largely unexplored.
Objectives: To investigate the roles of MTOR-autophagy axis in asthmatic airway injury, and the underlying mechanisms.
Methods: We analyzed the dysregulation of MTOR-autophagy signaling in airway epithelium from asthmatic patients and allergic mice. Mice with specific knockdown of mtor in airway epithelium and autophagy-related lc3b-/- mice were used. MTOR, autophagy, inflammation, cytokine expression were detected by electronic microscopy, immunofluorescence, immunohistochemistry, Western blotting, and ELISA.
Measurements and Main Results: MTOR activity was decreased, while autophagy and its hallmark MAP1LC3B/LC3B were elevated, in airway epithelium from asthmatic patients and allergic mice. Specific knockdown of mtor in mouse bronchial epithelium augmented, while deletion of lc3b diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by mtor deficiency was also ameliorated in lc3b-/- mice. Mechanistically, the induction of autophagy was later than the emergence of allergen-initiated inflammation, and mtor deficiency increased, while knockout of lc3b abolished, the cell death and production of pro-allergic IL33 in airways upon allergen challenge
Conclusions: These results demonstrate that allergen-initiated inflammation inactivates MTOR and induces autophagy in airway epithelium, which then promotes the epithelial cell death and IL33 production, eventually leading to the amplified and perpetuated inflammatory storm in asthma. Thus, activation of MTOR and/or inhibition of autophagy may serve as a therapeutic strategy for asthma.
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