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A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6

Title
A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6
Authors
Choi, JPKim, YSTae, YMChoi, EJHong, BSJeon, SGGho, YSZhu, ZKim, YK
POSTECH Authors
Gho, YS
Date Issued
Oct-2010
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Abstract
P>Background: Innate immune response by a viral pathogen-associated molecular pattern dsRNA modulates the subsequent development of adaptive immune responses. Although virus-associated asthma is characterized by noneosinophilic inflammation, the role of Th17 cell response in the development of virus-associated asthma is still unknown. Objective: To evaluate the role of the Th17 cell response and its underlying polarizing mechanisms in the development of an experimental virus-associated asthma. Methods: An experimental virus-associated asthma was created via airway sensitization with ovalbumin (OVA, 75 mu g) and a low (0.1 mu g) or a high (10 mu g) doses of synthetic dsRNA [polyinosine-polycytidylic acid
poly(I:C)]. Transgenic (IL-17-, IL-6-deficient mice) and pharmacologic [a vascular endothelial growth factor receptor (VEGFR) inhibitor] approaches were used to evaluate the roles of Th17 cell responses. Results: After cosensitization with OVA and low-dose poly(I:C), but not with high-dose poly(I:C), inflammation scores after allergen challenge were lower in IL-17-deficient mice than in wild-type (WT) mice. Moreover, inflammation enhanced by low-dose poly(I:C), but not by high-dose poly(I:C), was impaired in IL-6-deficient mice
this phenotype was accompanied by the down-regulation of IL-17 production from T cells from both lymph nodes and lung tissues. Airway exposure of low-dose poly(I:C) enhanced the production of VEGF and IL-6, and the production of IL-6 was blocked by treatment with a VEGFR inhibitor (SU5416). Moreover, the allergen-specific Th17 cell response and subsequent inflammation in the low-dose poly(I:C) model were impaired by the VEGFR inhibitor treatment during sensitization. Conclusions: Airway exposure of low-level dsRNA induces an allergen-specific Th17 cell response, which is mainly dependent on VEGF and IL-6.
Keywords
IL-6; noneosinophilic asthma; Th17; vascular endothelial growth factor; virus-associated asthma; ENDOTHELIAL GROWTH-FACTOR; TOLL-LIKE RECEPTOR-3; T-HELPER-CELLS; CHILDHOOD ASTHMA; T(H)17 CELLS; RIG-I; INFLAMMATION; INTERLEUKIN-17; ACTIVATION; DISTINCT
URI
http://oasis.postech.ac.kr/handle/2014.oak/25590
DOI
10.1111/J.1398-9995.2010.02369.X
ISSN
0105-4538
Article Type
Article
Citation
ALLERGY, vol. 65, no. 10, page. 1322 - 1330, 2010-10
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 GHO, YONG SONG
Dept of Life Sciences
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