title: Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.
abstract: Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Aida
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Igarashi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nunomiya
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Sato-Nishiwaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D016676:Macrophages, Alveolar / Q000378:metabolism; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010196:Pancreatic Elastase / Q000235:genetics / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D010196:Pancreatic Elastase
keywords: MafB; Pulmonary emphysema; alveolar macrophage; gene targeted mouse.; matrix metalloproteinase