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The Effects of Viral Components, Single-Stranded RNA and Double-Stranded RNA, on Allergen-Induced Airway Hyperresponsiveness and Airway Inflammation

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A1316 - The Effects of Viral Components, Single-Stranded RNA and Double-Stranded RNA, on Allergen-Induced Airway Hyperresponsiveness and Airway Inflammation
Author Block: S. Ashino1, H. Kitamura2, T. Akaba3, K. Takeyama3, J. Tamaoki3, J. Yagi1; 1Department of Microbiology and Immunology, Tokyo Women’s Medical University, Tokyo, Japan, 2Division of Functional Immunology, Institute of Genetic Medicine, Hokkaido University, Sapporo, Japan, 3First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Rationale:
Viral infection is one of the causes to exacerbate asthma. However, it has not been fully elucidated how a virus affects and alters pathological condition of asthma. It also remains unclear what kinds of viral components can be a trigger of asthma exacerbation. In this study, we investigated the effects of viral components, single stranded (ss) RNA and double stranded (ds) RNA which are ligands of Toll-like receptor (TLR) 7 and TLR3, respectively, on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) and airway inflammation in an experimental model of asthma.
Methods:
Wild-type C57BL/6 mice were sensitized with OVA emulsified in alum on days 0 and 14, and subsequently challenged with aerosolized OVA from days 28 to 30. On day 32, the mice were intratracheally administered two synthesized nucleotides, R848 and poly I:C, which mimic a viral component ssRNA and dsRNA, respectively. 24 hours after the exposure of the viral components, AHR and bronchoalveolar lavage fluid (BALF) cell composition were assessed. In addition, cytokine productions in the lung were analyzed.
Results:
Following OVA sensitization and challenge, the mice developed AHR and airway inflammation with eosinophil infiltration into the lung. Administration with ssRNA, R848, very slightly increased the AHR without any changes of the airway eosinophilia. On the other hand, the administration with dsRNA, poly I:C, markedly induced severe AHR with airway neutrophilia in addition to eosinophilia. It was also found that R848 treatment didn’t change any cytokine levels in the lung, whereas poly I:C treatment increased the levels of IFN-γ and IL-12 with substantial Th2 cytokines such as IL-4, IL-5, and IL-13. There was no synergistic effects of co-administration with R848 and poly I:C on the AHR and the airway inflammation.
Conclusions:
A viral component dsRNA, rather than ssRNA, is capable of inducing asthma exacerbation, suggesting that the activation of TLR3, but not TLR7, signaling pathway is associated.
This study represents a new insight that TLR3-mediated immune responses including pulmonary IFN-γ and IL-12 productions with airway neutrophilia can contribute viral infection-induced asthma exacerbation.
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