Journal
RESPIRATORY RESEARCH
Volume 14, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1465-9921-14-28
Keywords
Mast cells; Virus; Double-stranded RNA; Allergic asthma; Knockout mice
Categories
Funding
- JSPS KSKENHI [18591114]
Ask authors/readers for more resources
Background: Clinical studies showed the contribution of viral infection to the development of asthma. Although mast cells have multiple roles in the pathogenesis of allergic asthma, their role of in the virus-associated pathogenesis of asthma remains unknown. Most respiratory viruses generate double-stranded (ds) RNA during their replication. dsRNA provokes innate immune responses. We recently showed that an administration of polyinocinic polycytidilic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13. Methods: The effect of poly IC on allergen-induced airway eosinophilia was investigated for mast cell-conserved Kit(+/+) mice and -deficient Kit(W)/Kit(W-v) mice. The outcome of mast cell reconstitution was further investigated. Results: Airway eosinophilia and IL-13 production were augmented by poly IC in Kit(+/+) mice but not in Kit(W)/Kit(W-v) mice. When Kit(W)/Kit(W-v) mice were reconstituted with bone marrow-derived mast cells (BMMCs), the augmentation was restored. The augmentation was not induced in the mice systemically deficient for TIR domain-containing adaptor-inducing IFN-beta (TRIF) or interferon regulatory factor (IRF)-3, both mediate dsRNA-triggered innate immune responses. The augmentation was, however, restored in Kit(W)/Kit(W-v) mice reconstituted with TRIF-deficient or IRF-3-deficient BMMCs. Although leukotriene B-4 and prostaglandin D-2 are major lipid mediators released from activated mast cells, no their contribution was shown to the dsRNA-induced augmentation of airway eosinophilia. Conclusions: We conclude that mast cells contribute to dsRNA-induced augmentation of allergic airway inflammation without requiring direct activation of mast cells with dsRNA or involvement of leukotriene B-4 or prostaglandin D-2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available