2006 Fiscal Year Final Research Report Summary
Role of TGF-β1 derived from eosinophils in airway remodeling induced by repeated allergen challenge in mice
| Project/Area Number |
16616005
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
アレルギー
|
|---|
| Research Institution | Gifu Pharmaceutrical University |
|---|
Principal Investigator |
TANAKA Hiroyuki Gifu Pharm.Univ., Pharmacology, Associate Prof., 薬学部, 助教授 (70264695)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Keywords | asthma / Eosinophils / Remodeling / Allergy / Wound healing / Fibrosis |
|---|
| Research Abstract |
In the present study, we investigated the role of TGF-β1 derived from eosinophils in airway remodeling induced by repeated allergen challenge in mice. First, we examined the effect of anti-TGF-β1 neutralizing antibody on antigen-induced airway eosinophilic inflammation, airway remodeling and hyperresponsiveness in a mouse model of allergic asthma. As a result, this antibody administered during antigen inhalation for 3 weeks significantly augmented airway eosinophilia and antigen specific IgG1 antibody in serum but not airway hyperresponsiveness, although subepithelial fibrosis was clearly inhibited. In contrast, when it was administered during the first 10 days of antigen challenge, the antibody clearly enhanced the number of eosinophils in the bronchoalveolar lavage fluid (BALF) and serum antigen specific IgG1 levels but not subepithelial fibrosis, whereas it significantly inhibited subepithelial fibrosis when it was administered during the last 10 days of antigen challenge. These dat
… More
a strongly suggest that TGF-β1 is like a sword with double-edge for chronic airway inflammation induced by repeated antigen challenge.
Next, we investigated whether these findings are universal feature or not using the other asthma model induced by house dust mite, Dermatophagoides farinae (Der f). First, we established a mouse model of atopic asthma by repeated instillations of Der f into the mouse trachea without any adjuvant under the anesthesia. As a result, repeated instillations of the allergen can induce asthmatic phenotypes, such as airway hyperresponsiveness, airway eosinophilia, and airway remodeling, including subepithelial fibrosis. Furthermore, these characteristics are all abolished by the deficiency of interleukin-4 receptor alpha chain gene, indicating that the asthmatic phenotypes observed in this model are Th2 dependent.
Finally, we investigated whether TGF-β1 production is dependent on IL-4,IL-5 or IL-13 using gene-deficient mice. As a result, airway hyperresponsiveness is IL-4 and IL-13 dependent, airway eosinophilia is completely dependent on IL-5,TGF-β1 production in the airways and airway remodeling is dependent on IL-13.
These findings indicate that the production of TGF-β1 in the inflamed airways is dependent on the kind of inhaled allergen and environmental circumstance. Therefore, these data may contribute to the understandings of the development of airway remodeling and the strategy of the therapeutic approach for bronchial asthma. Less
|
Research Products
(12 results)
