title: Rhinovirus and dsRNA induce RIG-I-like receptors and expression of interferon β and λ1 in human bronchial smooth muscle cells.
abstract: Rhinovirus (RV) infections cause exacerbations and development of severe asthma highlighting the importance of antiviral interferon (IFN) defence by airway cells. Little is known about bronchial smooth muscle cell (BSMC) production of IFNs and whether BSMCs have dsRNA-sensing receptors besides TLR3. dsRNA is a rhinoviral replication intermediate and necrotic cell effect mimic that mediates innate immune responses in bronchial epithelial cells. We have explored dsRNA-evoked IFN-β and IFN-λ1 production in human BSMCs and potential involvement of TLR3 and RIG-I-like receptors (RLRs). Primary BSMCs were stimulated with 0.1-10 µg/ml dsRNA, 0.1-1 µg/ml dsRNA in complex with the transfection agent LyoVec (dsRNA/LyoVec; selectively activating cytosolic RLRs) or infected with 0.05-0.5 MOI RV1B. Both dsRNA stimuli evoked early (3 h), concentration-dependent IFN-β and IFN-λ1 mRNA expression, which with dsRNA/LyoVec was much greater, and with dsRNA was much less, after 24 h. The effects were inhibited by dexamethasone. Further, dsRNA and dsRNA/LyoVec concentration-dependently upregulated RIG-I and MDA5 mRNA and protein. dsRNA and particularly dsRNA/LyoVec caused IFN-β and IFN-λ1 protein production (24 h). dsRNA- but not dsRNA/LyoVec-induced IFN expression was partly inhibited by chloroquine that suppresses endosomal TLR3 activation. RV1B dose-dependently increased BSMC expression of RIG-I, MDA5, IFN-β, and IFN-λ1 mRNA. We suggest that BSMCs express functional RLRs and that both RLRs and TLR3 are involved in viral stimulus-induced BSMC expression of IFN-β and IFN-λ1.
authors: Unit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Jenny
authors: J
authors: Calvén
authors: Yuliana
authors: Y
authors: Yudina
authors: Lena
authors: L
authors: Uller
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D002738:Chloroquine / Q000494:pharmacology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D061251:Primary Cell Culture; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D011971:Receptors, Immunologic; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D002738:Chloroquine; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D003907:Dexamethasone; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D051196:Toll-Like Receptor 3; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495344:TLR3 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human
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