{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T22:36:00Z","timestamp":1781217360284,"version":"3.54.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Airway epithelial cell death and inflammation are pathological features of chronic obstructive pulmonary disease (COPD). Mechanistic target of rapamycin (MTOR) is involved in inflammation and multiple cellular processes, e.g., autophagy and apoptosis, but little is known about its function in COPD pathogenesis. In this article, we illustrate how MTOR regulates cigarette smoke (CS)\u2013induced cell death, airway inflammation, and emphysema. Expression of MTOR was significantly decreased and its suppressive signaling protein, tuberous sclerosis 2 (TSC2), was increased in the airway epithelium of human COPD and in mouse lungs with chronic CS exposure. In human bronchial epithelial cells, CS extract (CSE) activated TSC2, inhibited MTOR, and induced autophagy. The TSC2\u2013MTOR axis orchestrated CSE-induced autophagy, apoptosis, and necroptosis in human bronchial epithelial cells; all of which cooperatively regulated CSE-induced inflammatory cytokines IL-6 and IL-8 through the NF-\u03baB pathway. Mice with a specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly augmented airway inflammation and airspace enlargement in response to CS exposure, accompanied with enhanced levels of autophagy, apoptosis, and necroptosis in the lungs. Taken together, these data demonstrate that MTOR suppresses CS-induced inflammation and emphysema\u2014likely through modulation of autophagy, apoptosis, and necroptosis\u2014and thus suggest that activation of MTOR may represent a novel therapeutic strategy for COPD.<\/jats:p>","DOI":"10.4049\/jimmunol.1701681","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T16:50:21Z","timestamp":1520268621000},"page":"2571-2580","source":"Crossref","is-referenced-by-count":91,"title":["MTOR Suppresses Cigarette Smoke\u2013Induced Epithelial Cell Death and Airway Inflammation in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-0882","authenticated-orcid":false,"given":"Yong","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-2473","authenticated-orcid":false,"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Sen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-6322","authenticated-orcid":false,"given":"Hua-Qiong","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou-Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Chen","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Wen","family":"Lai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Pin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Min","family":"Ying","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Hao","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]},{"name":"State Key Laboratory of Respiratory Disease, Guangzhou Medical University , Guangzhou 510120,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou 310009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,15]]},"reference":[{"key":"2025030610142287900_r1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1164\/rccm.201204-0596PP","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary","volume":"187","author":"Vestbo","year":"2013","journal-title":"Am. 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