Journal Article

Transforming Growth Factor-Beta Promotes Rhinovirus Replication in Bronchial Epithelial Cells by Suppressing the Innate Immune Response

Green, Ben, Tatler, Amanda, Howarth, Peter H., Dennison, Patrick, Sammut, David, Jenkins, Gisli, Davies, Donna E., Kehagia, Valia, Holgate, Stephen T., Bedke, Nicole

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antibodies / Antibodies, Neutralizing - immunology / Asthma / Biology / Biomedical research / Blotting, Western / Bone morphogenetic proteins / Bronchi - cytology / Bronchi - immunology / Bronchi - virology / Cell cycle / Conditioning / Cyclin-dependent kinases / Cytokines / Double-stranded RNA / Electrophoresis, Polyacrylamide Gel / Enzyme-Linked Immunosorbent Assay / Epithelial cells / Epithelial Cells - cytology / Epithelial Cells - immunology / Epithelium / Fibroblasts / Gene expression / Growth factors / Health aspects / Hospitals / Humans / Immune response / Immune system / Immunity, Innate / Immunologic factors / Infection / Infections / Innate immunity / Interferon / Kinases / Medical research / Medicine / Real-Time Polymerase Chain Reaction / Replication / Respiratory syncytial virus / Reverse Transcriptase Polymerase Chain Reaction / Rhinovirus / Rhinovirus - physiology / Ribonucleic acid / RNA / Smad protein / Suppressor of Cytokine Signaling 1 Protein / Suppressor of Cytokine Signaling 3 Protein / Suppressor of Cytokine Signaling Proteins - antagonists & inhibitors / Suppressor of Cytokine Signaling Proteins - biosynthesis / Transforming Growth Factor beta - immunology / Transforming Growth Factor beta - physiology / Transforming growth factor- beta / Transforming growth factor-b / Transforming growth factors / Viral infections / Virus Replication - physiology