2012 Fiscal Year Final Research Report
Exploration ofmechanisms & new therapeutic targets for severe asthma
| Project/Area Number |
22390167
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Kagoshima University |
|---|
Principal Investigator |
INOUE Hiromasa 鹿児島大学, 大学院・医歯学総合研究科, 教授 (30264039)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUKUYAMA Satoru 九州大学, 大学病院, 助教 (50380530)
MAEYAMA Takashige 九州大学, 医学研究院, 助教 (40380456)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
NAKANISHI Yoichi 九州大学, 医学研究院, 教授 (20172356)
KUBO Masato 東京理科大学, 生命科学研究所, 教授 (40277281)
SUZUKI Atsushi 九州大学, 生体防御医学研究所, 教授 (30415195)
YOKOMIZO Takehiko 順天堂大学, 大学院・医学研究科, 教授 (60302840)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | 気管支喘息 / サイトカイン / ロイコトリエンB4 / インターロイキン13 |
|---|
| Research Abstract |
Effective treatment of severe asthma is a major unmet need. T helper (Th) 2 cytokines and lipid mediators, especially IL-13, are considered to play essential roles in pathophysiology of severe refractory asthma. For the acute exacerbation of asthma, the most common trigger is respiratory tract infection with viruses. We studied here the mechanisms underlying increased production of IL-13 in asthma and the pathogenesis of asthma exacerbations after viral infection. We hypothesized that Th1 cells could be a source of IL-13. IL-13 expression was induced after chronic stimulation of Th1 cells and IL-13 expression was regulated by the transcription factor E4BP4. Many RNA viruses, pathogenic for the respiratory tract, generate double stranded (ds)RNA during their replication. We found that synthetic dsRNA during sensitization augmented asthma phenotypes in a mouse model, which was associated with enhanced induction of IL-13-producing CD8 T cells. Costimulatory molecules B7-H1 (also known as PD-L1) plays a crucial role in the process. Impaired production of type III interferons (IFNs, IFN-λ) is related to the severity of asthma exacerbation. We found that dsRNA induces IFN-λproduction in airway epithelial cells and alveolar macrophages and that IL-13 suppresses the IFN-λexpression. These mechanisms may contribute to the impairment of the antiviral defense in asthmatics.
|
Research Products
(17 results)
-
[Journal Article] Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia2013
Author(s)
Matsunaga Y, Fukuyama S, Okuno T, Sasaki F, Matsunobu T, Asai Y, Matsumoto K, Saeki K, Oike M, Sadamura Y, Machida K, Nakanishi Y, Kubo M, Yokomizo T, Inoue H
-
Journal Title
DOI
Peer Reviewed
-
-
-
[Journal Article] The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells2011
Author(s)
Motomura Y, Kitamura H, Hijikata A, Matsunaga Y, Matsumoto K, Inoue H, Atarashi K, Hori S, Watarai H, Zhu J, Taniguchi M, Kubo M
-
Journal Title
Nat Immunol
Volume: 12(5)
Pages: 450-9
DOI
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
