| Project/Area Number |
12670758
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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 |
Pediatrics
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| Research Institution | Saga Medical School |
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Principal Investigator |
HAMASAKI Yuhei Facultyo of Medicine, Saga Medical School, Professor, 医学部, 教授 (10172967)
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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 |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | leukotriene C4 ; LTC4 / LTC4 synthase / bronchial asthma / alleray / ロ(ユトリエンC_4;LTC_4 / LTC4合成酵素 / LTC_4;ロイコトリエンC_4 |
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| Research Abstract |
It has been considered that leukotriene(LT)C4 is one of the most important mediators in the pathogenesis of allergic diseases including bronchial asthma. Recently, it has been demonstrated that the activities of synthesizing enzymes of LTs are genetically determined. We investigated the prevalence of A-C conversion in the promoter region of LTC4 synthase (-444bp up-stream from the initiation site of translation). Ten percents of patients with allergic diseases were C/C type and 60 % of patients were A/C type. On the other hands , the control subjects with C/C type were 0 % and those with A/C type were 27.3 %. These results supported a possibility that A-C conversion of LTC4 synthase in the promoter region was associated with the enzyme activity of LTC4 synthase. These results also indicate that the regulation of LTC4 synthase activity may contribute the pathogenesis of allergic diseases including bronchial asthma. We also investigated the inhibitory action of a variety of chemical substances on LT-synthesis using mast cell derived cultured cells (RBL ; rat basophilic leukemia) and found that (9- [4-acetyl-3-hydroxy-2-n-propylphenoxy methyl]-3 (1H-tetrazol-5-yl)-4H-pyrido[1,2-a] pyritnidin-4-one) ; AS-35, was potent inhibitor of LT synthase activity. In the patients with bronchial asthma, 5-lipoxygenase and LTC4 synthase, two pivotal enzymes of LT-synthesis, were up-regulated at the transcriptional level. These findings indicate that the transcriptional regulation of LTC4 synthase and 5-lipoxygenase plays an important role in the pathogenesis of allergic diseases in child hood.
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