| Project/Area Number |
12670555
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
NAKAMURA Hirotoshi Hamamatsu University School of Medicine, Medicine, Professor of Medicine, 医学部, 教授 (60164331)
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| Co-Investigator(Kenkyū-buntansha) |
SUDA Takafumi Hamamatsu University School of Medicine, Medicine, Assistant Professor, 医学部, 教授 (30291397)
SASAKI Shigekazu Hamamatsu University School of Medicine, Medicine, Associate Professor, 医学部, 教授 (20303547)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | alveolar macropharge / 25-hydroxyvitainin D3 lα-hydroxylase / sarcoidosis / lung cancer / nuclear receptor / CD36 / pcroxisome proliferator-activated receptor (PPAR)γ / anti-inflammation / peroxisome proliferator-activated receptor (PPAR)γ / 1αhydroxylase / PPARγ |
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| Research Abstract |
(1) Expression of the 25-hydroxyvitamin D3 lα-hydroxylase gene in human alveolar macrophages
We demonstrated expression of the 25-hydroxyvitamin D3 lα-hydroxylase (lαOHse) gene in human alveolar macrophages (AM) prepared from bronchoalveolar lavage cells by reverse transcription polymerase chain reaction (RT-PCR). The lα Hse-mRNA level measured by semiquantitative RT-PCR was five-fold higher in patients with sarcoidosis than control patients with other pulmonary disorders. There was a good correlation between the lα Ohse-mRNA level in bronchoalveolar lavage samples and the relative population of alveolar lymphocytes, the CD4/CD8 ratio, serum ACE, serum ionized calcium and the lα, 25-dihydroxylase D3/25-hydroxyvitamin D3 (25D3/1,25D3) ratio, suggesting that lα Ohse in AM was functional and significantly correlated with the activity of sarcoidosis and calcium metabolism.
Among patients with various pulmonary diseases, we found that the lα Ohse-mRNA in patients with lung carcinomas was sign
… More
ificantly enhanced, about twice the control. Correlation was observed between lα Ohse-mRNA level and the 25D3/I,25D3 ratio. Though not statistically significant, the lα Ohse-mRNA level in AM tended to increase in the patients with advanced stage.
(2) Expression and Function of Peroxisome Proliferator-Activated Receptor (PPAR) T in Human Alveolar Macrophages
Using RT-PCR, we demonstrated the expression of PPAR mRNAs in freshly isolated human AM. PPARα, β and γ were all expressed, but PPARγ was dominant. A specific ligand of PPARγ, 15-deoxy-D12,14prostaglandin J2 (15d-PGJ2), significantly decreased LPS-induced TNF-α production by Ams and markedly increased the expression of CD36 that mediates the phagocytosis of apoptotic neutrophils, an essential process for the resolution of inflammation. We confirmed that 15d-PGJ2-treated Ams showed a significantly increased phagocytosis of apoptotic neutrophils by in vitro phagocytosis assay. The data indicate that PPARγ in Ams play an anti-inflammatory role through inhibiting cytokine production and increasing their CD36 expression with the enhancement of the capacity to phagocytose apoptotic neulrophils. Less
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