Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.
e44580
Bedke, Nicole
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Sammut, David
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Green, Ben
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Kehagia, Valia
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Dennison, Patrick
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Jenkins, Gisli
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Tatler, Amanda
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Howarth, Peter H.
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Holgate, Stephen T.
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Davies, Donna E.
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6 September 2012
Bedke, Nicole
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Sammut, David
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Green, Ben
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Kehagia, Valia
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Dennison, Patrick
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Jenkins, Gisli
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Tatler, Amanda
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Howarth, Peter H.
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Holgate, Stephen T.
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Davies, Donna E.
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Bedke, Nicole, Sammut, David, Green, Ben, Kehagia, Valia, Dennison, Patrick, Jenkins, Gisli, Tatler, Amanda, Howarth, Peter H., Holgate, Stephen T. and Davies, Donna E.
(2012)
Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
PLoS ONE, 7 (9), .
(doi:10.1371/journal.pone.0044580).
(PMID:22970254)
Abstract
Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.
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Published date: 6 September 2012
Organisations:
Clinical & Experimental Sciences
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Local EPrints ID: 346650
URI: http://eprints.soton.ac.uk/id/eprint/346650
ISSN: 1932-6203
PURE UUID: dce46337-e0d8-4f3e-a5c3-f83a21b2a023
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Date deposited: 16 Jan 2013 12:06
Last modified: 15 Mar 2024 02:35
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Author:
Nicole Bedke
Author:
David Sammut
Author:
Ben Green
Author:
Valia Kehagia
Author:
Patrick Dennison
Author:
Gisli Jenkins
Author:
Amanda Tatler
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