by Nicole Bedke, David Sammut, Ben Green, Valia Kehagia, Patrick Dennison, Gisli Jenkins, Amanda Tatler, Peter H. Howarth, Stephen T. Holgate, Donna E. Davies
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-ß, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-ß2 increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-ß antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-ß2 levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-ß on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-ß and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-ß contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.