title: 4-Hydroxy-2-nonenal induces chronic obstructive pulmonary disease-like histopathologic changes in mice.
abstract: The α,β-unsaturated aldehyde 4-hydroxy-2-nonenal (4-HNE) is an endogenous product of oxidative stress that is found at increased levels in the lungs of patients with chronic obstructive pulmonary disease (COPD) and animal models of this lung disorder. In the present study, levels of 4-HNE adducts were increased in two different mouse models of COPD. Challenging lungs with 4-HNE enlarged the airspace and induced goblet cell metaplasia of the airways in mice, two characteristics of COPD. 4-HNE induced the accumulation of inflammatory cells expressing high levels of MMP-2 and MMP-9. Our results indicate that 4-HNE production during oxidative stress is a key pathway in the pathogenesis of COPD.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takimoto
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hirata
authors.forename: Yozo
authors.initials: Y
authors.lastname: Kashiwa
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.forename: Sho
authors.initials: S
authors.lastname: Goya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.forename: Toru
authors.initials: T
authors.lastname: Kumagai
authors.forename: Isao
authors.initials: I
authors.lastname: Tachibana
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D000447:Aldehydes / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000447:Aldehydes; D008666:Metalloendopeptidases; C027576:4-hydroxy-2-nonenal