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-β, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following...

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Main Authors: Nicole Bedke, David Sammut, Ben Green, Valia Kehagia, Patrick Dennison, Gisli Jenkins, Amanda Tatler, Peter H Howarth, Stephen T Holgate, Donna E Davies
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044580&type=printable
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author Nicole Bedke
David Sammut
Ben Green
Valia Kehagia
Patrick Dennison
Gisli Jenkins
Amanda Tatler
Peter H Howarth
Stephen T Holgate
Donna E Davies
author_facet Nicole Bedke
David Sammut
Ben Green
Valia Kehagia
Patrick Dennison
Gisli Jenkins
Amanda Tatler
Peter H Howarth
Stephen T Holgate
Donna E Davies
author_sort Nicole Bedke
collection DOAJ
description 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-β, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-β(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-β antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-β(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-β on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-β and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-β contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.
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issn 1932-6203
language English
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
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series PLoS ONE
spelling doaj-art-b82d414dff97451b8bb768e3c0f7ae2e2025-08-20T03:26:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4458010.1371/journal.pone.0044580Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.Nicole BedkeDavid SammutBen GreenValia KehagiaPatrick DennisonGisli JenkinsAmanda TatlerPeter H HowarthStephen T HolgateDonna E DaviesRhinovirus (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-β, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-β(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-β antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-β(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-β on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-β and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-β contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044580&type=printable
spellingShingle Nicole Bedke
David Sammut
Ben Green
Valia Kehagia
Patrick Dennison
Gisli Jenkins
Amanda Tatler
Peter H Howarth
Stephen T Holgate
Donna E Davies
Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
PLoS ONE
title Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
title_full Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
title_fullStr Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
title_full_unstemmed Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
title_short Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
title_sort transforming growth factor beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044580&type=printable
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