| Title | Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response. | ||
| Author | Bedke, Nicole; Sammut, David; Green, Ben; Kehagia, Valia; Dennison, Patrick; Jenkins, Gisli; Tatler, Amanda; Howarth, Peter H; Holgate, Stephen T; Davies, Donna E | ||
| Journal | PLoS One | Publication Year/Month | 2012 |
| PMID | 22970254 | PMCID | PMC3435262 |
| Affiliation | 1.Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom. | ||
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-beta, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-beta(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-beta antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-beta(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-beta on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-beta and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-beta contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.