Project/Area Number |
21592177
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Otorhinolaryngology
|
Research Institution | Nagoya City University |
Principal Investigator |
SUZUKI Motohiko 名古屋市立大学, 大学院・医学研究科, 准教授 (50326138)
|
Co-Investigator(Kenkyū-buntansha) |
HIDA Hideki 名古屋市立大学, 大学院・医学研究科, 教授 (00305525)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
Keywords | 鼻科学 / アレルギー / siRNA / RNA干渉 / 樹状細胞 / CD40 |
Research Abstract |
We previously reported that systemic administration of CD40 siRNA attenuated allergic symptoms. However, this is an allergen-nonspecific fashion. Therefore, we tried to develop a new allergen-specific therapy for allergy using CD40-silenced and allergen-pulsed dendritic cells(DCs). Bone marrow-derived DCs were transfected with CD40 siRNA and pulsed with ovalbumin(OVA). Mice were sensitized intraperitoneally with OVA and keyhole limpet hemocyanin, followed by intranasal challenge with these allergens. Mice were treated with CD40-silenced and OVA-pulsed DCs(CD40-silenced OVA DCs) before allergic sensitization. The mice receiving CD40-silenced OVA DCs inhibited allergic symptoms caused by OVA challenge, as well as anti-OVA IgE levels in sera. Also, CD40-silenced OVA DCs suppressed eosinophil infiltration at the nasal septum, OVA-specific T-cell responses, and T-cell production of IL-4 and IL-5 after stimulation with OVA. However, CD40-silenced OVA DCs did not inhibit keyhole limpet hemocyanin-induced allergy, suggesting that CD40-silenced OVA DCs induce allergen-specific tolerance. I reported that dendritic cells, which were transfected with CD40 siRNA and pulsed with ovalbumin(OVA), inhibited allergic rhinitis induced by OVA antigen but not the other antigens, suggesting that this is antigen-specific therapy.
|