Role of transcription factor MafB in alveolar macrophages of smoking-induced emphysema
| Project/Area Number |
16590733
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Yamagata University |
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Principal Investigator |
SHIBATA Yoko Yamagata University, School of Medicine, Instructor, 医学部, 助手 (60333978)
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| Co-Investigator(Kenkyū-buntansha) |
SATA Makoto Yamagata University, School of Medicine, Assistant Professor, 医学部, 講師 (00280892)
TAKABATAKE Noriaki Yamagata University, School of Medicine, Instructor, 医学部, 助手 (80344795)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | alveolar macrophage / transcription factor / MafB / cigarette smoking / pulmonary emphysema |
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| Research Abstract |
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 days/week) for 6 months. Development of pulmonary emphysema in 6-months' 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.
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Report
(3 results)
Research Products
(2 results)
