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Int J Biol Sci 2014; 10(8):882-894. doi:10.7150/ijbs.8737

Research Paper

Inhibition of Elastase-Pulmonary Emphysema in Dominant-Negative MafB Transgenic Mice

Yasuko Aida, Yoko Shibata, Shuichi Abe, Sumito Inoue, Tomomi Kimura, Akira Igarashi, Keiko Yamauchi, Keiko Nunomiya, Hiroyuki Kishi, Takako Nemoto, Masamichi Sato, Michiko Sato-Nishiwaki, Hiroshi Nakano, Kento Sato, Isao Kubota

Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

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.

Keywords: Pulmonary emphysema, MafB, alveolar macrophage, matrix metalloproteinase, gene targeted mouse.

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How to cite this article:
Aida Y, Shibata Y, Abe S, Inoue S, Kimura T, Igarashi A, Yamauchi K, Nunomiya K, Kishi H, Nemoto T, Sato M, Sato-Nishiwaki M, Nakano H, Sato K, Kubota I. Inhibition of Elastase-Pulmonary Emphysema in Dominant-Negative MafB Transgenic Mice. Int J Biol Sci 2014; 10(8):882-894. doi:10.7150/ijbs.8737. Available from http://www.ijbs.com/v10p0882.htm