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Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary pisease epithelium: role of endosomal TLR3 and cytosolic RIG-I-Like helicases

Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary pisease epithelium: role of endosomal TLR3 and cytosolic RIG-I-Like helicases
Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary pisease epithelium: role of endosomal TLR3 and cytosolic RIG-I-Like helicases
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 ?g/ml) or RIG-I-like helicases (dsRNA-LyoVec, 0.1-10 ?g/ml). Cytokine mRNA and protein were determined (RTqPCR; ELISA). Results: dsRNA dose-dependently evoked cytokine gene overproduction of TSLP, CXCL8 and TNF-? in COPD-BEC compared to HBEC. This was confirmed using RV16 infection. IFN-? 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-?, and IFN-?. Stimulation of cytosolic viral sensors (RIG-I-like helicases) with dsRNA-LyoVec increased production of CXCL8, TNF-?, and IFN-?, 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-? and CXCL8 involves endosomal TLR3 and cytosolic RIG-I-like helicases and so does the generation of IFN-? in COPD-BEC. RV16 and dsRNA-induced epithelial TSLP may contribute to pathogenic effects at exacerbations and development of COPD.
1662-811X
Calvén, Jenny
594ac20e-547b-432e-b73f-1646a69f0b40
Yudina, Yulyana
353ed6a2-2c54-487f-b647-0900d706c709
Hallgren, Oskar
ee922ba8-246c-458e-ad43-01c567f7b1e4
Westergren-Thorsson, Gunilla
edaff1a5-ae3a-4721-93bd-a15ca4b5f972
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Brandelius, Angelica
f799da7b-9f91-46ef-88c0-8ce25f104d26
Uller, Lena
e7a49820-e65d-45e1-857e-ac2918e683b4
Calvén, Jenny
594ac20e-547b-432e-b73f-1646a69f0b40
Yudina, Yulyana
353ed6a2-2c54-487f-b647-0900d706c709
Hallgren, Oskar
ee922ba8-246c-458e-ad43-01c567f7b1e4
Westergren-Thorsson, Gunilla
edaff1a5-ae3a-4721-93bd-a15ca4b5f972
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Brandelius, Angelica
f799da7b-9f91-46ef-88c0-8ce25f104d26
Uller, Lena
e7a49820-e65d-45e1-857e-ac2918e683b4

Calvén, Jenny, Yudina, Yulyana, Hallgren, Oskar, Westergren-Thorsson, Gunilla, Davies, Donna E., Brandelius, Angelica and Uller, Lena (2011) Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary pisease epithelium: role of endosomal TLR3 and cytosolic RIG-I-Like helicases. Journal of Innate Immunity. (doi:10.1159/000329131). (PMID:21691053) (In Press)

Record type: Article

Abstract

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 ?g/ml) or RIG-I-like helicases (dsRNA-LyoVec, 0.1-10 ?g/ml). Cytokine mRNA and protein were determined (RTqPCR; ELISA). Results: dsRNA dose-dependently evoked cytokine gene overproduction of TSLP, CXCL8 and TNF-? in COPD-BEC compared to HBEC. This was confirmed using RV16 infection. IFN-? 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-?, and IFN-?. Stimulation of cytosolic viral sensors (RIG-I-like helicases) with dsRNA-LyoVec increased production of CXCL8, TNF-?, and IFN-?, 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-? and CXCL8 involves endosomal TLR3 and cytosolic RIG-I-like helicases and so does the generation of IFN-? in COPD-BEC. RV16 and dsRNA-induced epithelial TSLP may contribute to pathogenic effects at exacerbations and development of COPD.

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Accepted/In Press date: 20 June 2011
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 194715
URI: https://eprints.soton.ac.uk/id/eprint/194715
ISSN: 1662-811X
PURE UUID: f5f4dff8-4ea4-485d-b918-7bf155bfa498
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 09 Aug 2011 16:02
Last modified: 24 May 2019 00:39

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Contributors

Author: Jenny Calvén
Author: Yulyana Yudina
Author: Oskar Hallgren
Author: Gunilla Westergren-Thorsson
Author: Donna E. Davies ORCID iD
Author: Angelica Brandelius
Author: Lena Uller

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