title: Attenuation of Cigarette Smoke-Induced Emphysema in Mice by Apolipoprotein A-1 Overexpression.
abstract: Chronic inflammation, oxidative stress, and proteolysis participate primarily in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. COPD is a highly prevalent smoking-related disease for which no effective therapy exists to improve the disease course. Although apolipoprotein A-1 (ApoA1) has antiinflammatory and antioxidant properties as well as cholesterol efflux potential, its role in cigarette smoke (CS)-induced emphysema has not been determined. Therefore, we investigated whether human ApoA1 transgenic (TG) mice, with conditionally induced alveolar epithelium to overexpress ApoA1, are protected against the CS-induced lung inflammatory response and development of emphysema. In this study, ApoA1 levels were significantly decreased in the lungs of patients with COPD and in the lungs of mice exposed to CS. ApoA1 TG mice did not develop emphysema when chronically exposed to CS. Compared with the control TG mice, ApoA1 overexpression attenuated lung inflammation, oxidative stress, metalloprotease activation, and apoptosis in CS-exposed mouse lungs. To explore a plausible mechanism of antiapoptotic activity of ApoA1, alveolar epithelial cells (A549) were treated with CS extract (CSE). ApoA1 prevented CSE-induced translocation of Fas and downstream death-inducing signaling complex into lipid rafts, thereby inhibiting Fas-mediated apoptosis. Taken together, the data showed that ApoA1 overexpression attenuated CS-induced lung inflammation and emphysema in mice. Augmentation of ApoA1 in the lung may have therapeutic potential in preventing smoking-related COPD/emphysema.
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Chorong
authors.initials: C
authors.lastname: Kim
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kim
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Myoung Won
authors.initials: MW
authors.lastname: Lee
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Paik
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: An Soo
authors.initials: AS
authors.lastname: Jang
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Do Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: 2 Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, Hannam-dong, Yongsan-gu, Seoul; and.
authors.forename: Sootaek
authors.initials: S
authors.lastname: Uh
authors.affiliation: 3 Division of Allergy and Respiratory Medicine, Soonchunhyang University Cheonan Hospital, Bongmyeong-dong, Cheonan, Chungcheongnam-do, South Korea.
authors.forename: Yonghoon
authors.initials: Y
authors.lastname: Kim
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D059748:Proteolysis; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; C491901:FAS protein, human; D012906:Smoke; D019014:fas Receptor; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: apolipoprotein A1; apoptosis; emphysema; lipid raft; smoking