title: Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.
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-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.
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bedke
authors.forename: David
authors.initials: D
authors.lastname: Sammut
authors.forename: Ben
authors.initials: B
authors.lastname: Green
authors.forename: Valia
authors.initials: V
authors.lastname: Kehagia
authors.forename: Patrick
authors.initials: P
authors.lastname: Dennison
authors.forename: Gisli
authors.initials: G
authors.lastname: Jenkins
authors.forename: Amanda
authors.initials: A
authors.lastname: Tatler
authors.forename: Peter H
authors.initials: PH
authors.lastname: Howarth
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000821:virology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D057134:Antibodies, Neutralizing; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016212:Transforming Growth Factor beta