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MDA5 and TLR3 initiate pro-inflammatory signaling pathways leading to rhinovirus-induced airways inflammation and hyperresponsiveness
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نویسنده
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wang q. ,miller d.j. ,bowman e.r. ,nagarkar d.r. ,schneider d. ,zhao y. ,linn m.j. ,goldsmith a.m. ,bentley j.k. ,sajjan u.s. ,hershenson m.b.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 5
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چکیده
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Rhinovirus (rv),a single-stranded rna picornavirus,is the most frequent cause of asthma exacerbations. we previously demonstrated in human bronchial epithelial cells that melanoma differentiation-associated gene (mda)-5 and the adaptor protein for toll-like receptor (tlr)-3 are each required for maximal rv1b-induced interferon (ifn) responses. however,in vivo,the overall airway response to viral infection likely represents a coordinated response integrating both antiviral and pro-inflammatory pathways. we examined the airway responses of mda5- and tlr3-deficient mice to infection with rv1b,a minor group virus which replicates in mouse lungs. mda5 null mice showed a delayed type i ifn and attenuated type iii ifn response to rv1b infection,leading to a transient increase in viral titer. tlr3 null mice showed normal ifn responses and unchanged viral titers. further,rv-infected mda5 and tlr3 null mice showed reduced lung inflammatory responses and reduced airways responsiveness. finally,rv-infected mda5 null mice with allergic airways disease showed lower viral titers despite deficient ifn responses,and allergic mda5 and tlr3 null mice each showed decreased rv-induced airway inflammatory and contractile responses. these results suggest that,in the context of rv infection,binding of viral dsrna to mda5 and tlr3 initiates pro-inflammatory signaling pathways leading to airways inflammation and hyperresponsiveness. © 2011 wang et al.
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آدرس
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department of molecular and integrative physiology,university of michigan medical school,ann arbor,mi, United States, department of internal medicine,university of michigan medical school,ann arbor,mi,united states,department of microbiology and immunology,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of molecular and integrative physiology,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States, department of molecular and integrative physiology,university of michigan medical school,ann arbor,mi,united states,department of pediatrics and communicable diseases,university of michigan medical school,ann arbor,mi, United States
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Authors
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