Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.
Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.
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DOI：
10.7150/ijbs.8737
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发表时间：
2014
影响因子：
9.2
通讯作者：
Kubota I
中科院分区：
文献类型：
--
作者：
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
肺泡巨噬细胞（AM）在慢性阻塞性肺疾病（COPD）的发病机制中发挥着重要作用。我们之前证明了暴露于香烟烟雾的小鼠 AM 中转录因子 MafB 的上调。本研究的目的是阐明 MafB 在肺气肿发展中的作用。将猪胰腺弹性蛋白酶给予野生型 (WT) 和显性失活 (DN)-MafB 转基因 (Tg) 小鼠，其中 MafB 活性仅在巨噬细胞中受到抑制。我们测量了支气管肺泡灌洗 (BAL) 细胞的平均线性截距并进行了细胞差异分析，使用流式细胞术进行表面标记分析，并使用基质金属蛋白酶 (MMP)-9 和 MMP-12 抗体进行免疫组织化学染色。与处理的 WT 小鼠相比，弹性蛋白酶处理的 DN-MafB Tg 小鼠的肺部空腔扩大受到显着抑制。 DN-MafB Tg 小鼠中具有突出伪足的 AM 减少。在 DN-MafB Tg 小鼠的 BAL 中，F4/80 中度阳性和 CD11b 弱或中度阳性的细胞数量（被认为是成熟 AM 的细胞亚群）减少。此外，DN-MafB Tg 小鼠的 BAL 细胞中 MMP-9 和 -12 显着下调。由于 MMP 会加剧肺气肿，因此 MafB 可能通过改变巨噬细胞的成熟和 MMP 表达参与肺气肿的发展。
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.
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DOI：
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