期刊
JOURNAL OF INNATE IMMUNITY
卷 4, 期 1, 页码 86-99出版社
KARGER
DOI: 10.1159/000329131
关键词
Chronic obstructive pulmonary disease; Rhinovirus; Thymic stromal lymphopoietin; TLR3
类别
资金
- Medical Research Council [G0501506] Funding Source: Medline
- MRC [G0501506] Funding Source: UKRI
- Medical Research Council [G0501506] Funding Source: researchfish
Background: Rhinovirus (RV)-induced chronic obstructive pulmonary disease (COPD) exacerbations exhibit TH2-like inflammation. We hypothesized that RV-infected bronchial epithelial cells (BEC) overproduce TH2-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 mu g/ml) or RIG-I-like helicases (dsRNA-LyoVec, 0.1-10 mu g/ml). Cytokine mRNA and protein were determined (RTqPCR; ELISA). Results: dsRNA dose-dependently evoked cytokine gene overproduction of TSLP, CXCL8 and TNF-alpha in COPD-BEC compared to HBEC. This was confirmed using RV16 infection. IFN-beta 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-alpha, and IFN-alpha. Stimulation of cytosolic viral sensors (RIG-I-like helicases) with dsRNA-LyoVec increased production of CXCL8, TNF-alpha, and IFN-beta, 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-alpha and CXCL8 involves endosomal TLR3 and cytosolic RIG-I-like helicases and so does the generation of IFN-beta in COPD-BEC. RV16 and dsRNA-induced epithelial TSLP may contribute to pathogenic effects at exacerbations and development of COPD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据