| Project/Area Number |
11670323
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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 |
Immunology
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| Research Institution | Saga Medical School (2000)
Kyushu University (1999) |
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Principal Investigator |
IZUHARA Kenji Saga Medical School, Dept.Biochem., Professor, 医学部, 教授 (00270463)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Masato Sci.Univ.Tokyo, Res.Inst.Biol.Sci., Assoc.Professor, 生命科学研究所, 助教授 (40277281)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | interleukin-13 / allergy / single nucleotide polymorphism / bronchial asthma / signal transduction / interleukin-13 receptor / Tyk2 / STAT3 / インターロイキン4 / 気道 |
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| Research Abstract |
We investigated the genetic role of the IL-13 gene in the pathogenesis of allergic diseases. We found a novel single nucleotide polymorphism (SNP) which substitutes glutamine at 110 for arginine. The incidence of glutamine was higher than arginine in both atopic and non-atopic asthma patients. Serum level of IL-13 was also higher in the glutamine type. These results suggest that the IL-13 gene is an asthma-causing gene.
To identify the target cells of IL-13 in lung, we generated anti-IL-13Rα1 antibody, and performed immunohistochemistry. It turned out that IL- 13Rα1 and IL-4Rα, both of which are the components of the IL-13R highly expressed on bronchial epithelial cells and bronchial smooth muscle cells. These results showed that these cells are main target cells of IL-13 in the lung tissue.
We next analyzed the signal transduction mechanism of IL-13 using various types of IL- 13Rα1. Consequently, it was revealed that Tyk2 bound to the Box1 region close to its transmembrane domain, IL-13 activated STAT3 in addition to STAT6, and STAT3 bound to the tyrosine residues close to its C-terminus.
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