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http://purl.uniprot.org/citations/21691053http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Rhinovirus (RV)-induced chronic obstructive pulmonary disease (COPD) exacerbations exhibit TH(2)-like inflammation. We hypothesized that RV-infected bronchial epithelial cells (BEC) overproduce TH(2)-switching hub cytokine, thymic stromal lymphopoietin (TSLP) in COPD.

Methods

Primary BEC from healthy (HBEC) and from COPD donors (COPD-BEC) were grown in 12-well plates, infected with RV16 (0.5-5 MOI) or stimulated with agonists for either toll-like receptor (TLR) 3 (dsRNA, 0.1-10 μg/ml) or RIG-I-like helicases (dsRNA-LyoVec, 0.1-10 μg/ml). Cytokine mRNA and protein were determined (RTqPCR; ELISA).

Results

dsRNA dose-dependently evoked cytokine gene overproduction of TSLP, CXCL8 and TNF-α in COPD-BEC compared to HBEC. This was confirmed using RV16 infection. IFN-β induction did not differ between COPD-BEC and HBEC. Endosomal TLR3 inhibition by chloroquine dose-dependently inhibited dsRNA-induced TSLP generation and reduced generation of CXCL8, TNF-α, and IFN-β. Stimulation of cytosolic viral sensors (RIG-I-like helicases) with dsRNA-LyoVec increased production of CXCL8, TNF-α, and IFN-β, but not TSLP.

Conclusions

Endosomal TLR3-stimulation, by dsRNA or RV16, induces overproduction of TSLP in COPD-BEC. dsRNA- and RV-induced overproduction of TNF-α and CXCL8 involves endosomal TLR3 and cytosolic RIG-I-like helicases and so does the generation of IFN-β in COPD-BEC. RV16 and dsRNA-induced epithelial TSLP may contribute to pathogenic effects at exacerbations and development of COPD."xsd:string
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http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Davies D.E."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Hallgren O."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Westergren-Thorsson G."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Uller L."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Yudina Y."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Brandelius A."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/author"Calven J."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/name"J Innate Immun"xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/pages"86-99"xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/title"Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary disease epithelium: role of endosomal TLR3 and cytosolic RIG-I-like helicases."xsd:string
http://purl.uniprot.org/citations/21691053http://purl.uniprot.org/core/volume"4"xsd:string
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