Enhanced expression of MafB inhibits macrophage apoptosis induced by cigarette smoke exposure
Enhanced expression of MafB inhibits macrophage apoptosis induced by cigarette smoke exposure
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DOI：
10.1165/rcmb.2006-0248oc
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Kubota, Isao
中科院分区：
文献类型：
--
作者：
Machiya, Jun-ichi;Shibata, Yoko;Kubota, Isao
在吸烟者的肺部，由于自由基和氧化剂，包括过氧化脂质(LPO)的增加，氧化应激增加。在这种环境中，肺泡巨噬细胞(AM)的功能发生了改变，其存活时间因未知的机制而延长。虽然AM的功能可能受各种转录因子的调节，但它们在吸烟者中的表达和作用尚未阐明。因此，我们利用CS暴露的小鼠模型研究了它们的表达。8周龄雄性B6C3F1小鼠全身暴露于CS(2支/只/天，5d/wk)6mo。形态计量学分析证实6-mo-CS染毒小鼠发生肺气肿。在所研究的转录因子中，只有MafB在CS暴露的小鼠AM中上调。小鼠AM中MafB与Maf识别元件的DNA结合能力也增强。CS染毒小鼠肺组织中LPO明显升高。由于LPO的最终产物4-羟基-2-壬烯醛可增强巨噬细胞系MafB的表达及其转录活性，推测LPO相关的氧化应激参与了CS暴露肺MafB表达的机制。此外，我们建立了一个能够过表达MafB的巨噬细胞系，从而阐明了MafB的作用。强制表达MafB可提高细胞存活率，减少CS提取物诱导的细胞凋亡。这些结果表明，氧化应激增强MafB的表达抑制了肺组织AM细胞的死亡，延长了其存活时间。
In the lungs of smokers, oxidative stress rises due to increase of free radicals and oxidants, including lipid peroxide (LPO). The functions of alveolar macrophages (AMs) are altered in such an environment, and their survival is prolonged against toxicities of cigarette smoke (CS) by an unknown mechanism. Whereas functions of AMs are potentially regulated by various transcriptional factors, their expressions and roles in smoking individuals have not been elucidated. Therefore, we investigated their expressions using murine model of CS exposure. Eight-week-old male B6C3F1 mice were whole-bodily exposed to CS (2 cigarettes/mouse/day, 5 d/wk) for 6 mo. Development of pulmonary emphysema in 6-mo CS-exposed mice was confirmed by a morphometric analysis. Among the transcriptional factors investigated, only MafB was upregulated in AMs from CS-exposed mice. DNA binding capacity of MafB for Maf recognition element was also increased in AMs from those mice. LPO was increased significantly in the lungs of CS-exposed mice. Because the end product of LPO, 4-hydroxy-2-nonenal, enhanced MafB expression and its transcriptional activity in a cultured macrophage cell line, LPO-related oxidative stress was suggested to be involved in the mechanism of MafB expression in CS-exposed lung. Furthermore, we established a macrophage cell line that can overexpress MafB and thereby clarify the role of MafB. Forced expression of MafB heightened cell viability and attenuated the occurrence of apoptosis in cells treated with CS-extract. These results suggest that enhanced MafB expression by oxidative stress inhibits AM cell death and prolongs their survival in the CS-exposed lung.