| Project/Area Number |
09670611
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
SUEMURA Masaki Osaka University Medical School, Associate Professor, 医学部, 助教授 (70144459)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KATADA Yoshinobu Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
TANAKA Toshio Osaka University Medical School, Assistant Professor, 医学部, 助手 (40273651)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | Bronchial asthma / type I allergy / Th2 cells / IgE / IL-4 / IL-4 receptor / beta2-adrenoceptor / eosinophil / β2-アドレナリン受容体 / アトピー / IL-4阻容剤 / I型アレルギー性疾患 / Th_1細胞 / Th_2細胞 / IL-6 / 抗原提示細胞 |
|---|
| Research Abstract |
Preferential development of Th2 cells and its therapeutic regulation in bronchial asthma
In bronchial asthma, a representative disease of type I allergy, allergen specific Th2 cells are preferentially differentiated and play central roles on the formation of IgE responses, organ hyper-reactivity and allergic inflammation.In this study what determinates might be responsible for such T cell differentiation and whether regulation of differentiation of Th2 cells through the manipulation of the Th2 cytokines caused an inhibition of development of type I allergic diseases were asked.
The expression of cytokine and polymorphisms of candidate genes, which might lead to Th2 preferential differentiation was examined.In hyper IgE status, it was found that IL-6 was over-produced by peripheral monocytes and serum level of IL-18 was elevated.To reveal whether or not these cytokines would function in the T cell differentiation, IL-6 gene knock-out mice or atopic dermatitis-model mice was employed.The results indicate that these cytokines might be negative regulatory cytokines in the Th2 development.Analyses of gene polymorphisms including 5'IL-4 regulatory region, IL-4 receptor or beta2-adrenoceptor exon genes showed that each polymorphism by itself might not be related to atopic diseases.However, it is possible that the combination of gene polymorphisms relate to the onset of the diseases, which are now in progress.
In order to find out compounds with the inhibitory activity of IL-4 function, many chemical compounds were screened in murine IgE synthesis system.And compound #8921 was found to suppress specifically IgE antibody responses, as well as Th2 cell differentiation.In murine asthma model, it suppressed serum IgE antibody levels and the infiltration of inflammatory cells, especially eosinophils, in the lung as assessed by broncho alveolar lavage.Detailed analysis of the action of compound #8921 is under progress.
|
