| Project/Area Number |
21591290
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
HARADA Michsihige 独立行政法人理化学研究所, 免疫制御研究グループ, 研究員 (20333487)
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| Co-Investigator(Renkei-kenkyūsha) |
TAMARI Mayumi 独立行政法人理化学研究所, 呼吸器疾患研究チーム, チームリーダー (00217184)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | TSLP / 遺伝子多型 / ウイルス感染刺激 / 気道上皮細胞 / 薬理遺伝学 / 呼吸機能 / ウイルス / アレルギー・ぜんそく / SNPs / 気管支喘息 / 相関解析 / 重症度 / アレルギー疾患 |
|---|
| Research Abstract |
Thymic stromal lymphopoietin(TSLP) triggers dendritic cell-mediated T helper(Th) 2 inflammatory responses. We investigated whether TSLP-polymorphisms could affect the susceptibility to and clinical phenotypes of bronchial asthma. We selected three Tag SNPs and conducted association studies of the TSLP gene using two independent populations(639 childhood atopic asthma patients and 838 controls, and 641 adult asthma patients and 376 controls, respectively). We further examined effects of corticosteroids and a long-acting b2-agonist(LABA)(salmeterol) on expression levels of the TSLP gene in response to poly(I : C) in NHBE. We found promoter polymorphisms, rs3806933 and rs2289276, significantly associated with disease susceptibility in both childhood atopic and adult asthma. The functional SNP rs3806933 was associated with asthma(meta-analysis, P=0.000056 ; odds ratio, 1.29 ; 95% confidence interval, 1.14-1.47). A genotype of rs2289278 was correlated with pulmonary function. We also found that the induction of TSLP mRNA and protein expression induced by poly(I : C) in NHBE was synergistically impaired by a corticosteroid and salmeterol. TSLP variants are significantly associated with bronchial asthma and pulmonary function. Thus, TSLP might be a therapeutic target molecule for combination therapy.
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