BACKGROUND: IL-13 is key mediator of allergic inflammation in asthmatic patients. We have previously shown that the decoy receptor IL-13 receptor (IL-13R) α2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13Rα2 can be regulated by IFN-γ, a type II interferon, we hypothesized that innate antiviral responses characterized by type I interferon expression can also induce IL-13Rα2 expression. OBJECTIVE: We sought to induce an innate antiviral response in primary fibroblasts using exposure to double-stranded RNA (dsRNA) and to examine the expression and function of IL-13Rα2. METHODS: Primary human fibroblasts were cultured from endobronchial biopsy specimens obtained from healthy or asthmatic volunteers and challenged with dsRNA. Upregulation of IL-13Rα2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13Rα2 protein expression was measured by using fluorescence-activated cell sorting. Eotaxin release was determined by means of ELISA. RESULTS: Direct treatment with IFN-β led to an upregulation of IL-13Rα2. Exposure to dsRNA rapidly induced IFN-β mRNA in fibroblasts, and this was followed by significant induction of IL-13Rα2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A neutralizing antibody to the IFN-α/β receptor blocked cell-surface expression of IL-13Rα2 in the presence of dsRNA. Pretreatment of fibroblasts with dsRNA led to attenuation of IL-13-stimulated eotaxin production. However, the presence of an IL-13Rα2 neutralizing antibody restored IL-13-stimulated eotaxin production in dsRNA-treated cells. CONCLUSION: IFN-β induces IL-13Rα2 expression, leading to a consequential suppression of responsiveness to IL-13. These data suggest cross-talk between TH1 and TH2 pathways and point to an immunomodulatory role for IL-13Rα2 in human bronchial fibroblasts during viral infection.
BACKGROUND:IL-13 is key mediator of allergic inflammation in asthmatic patients. We have previously shown that the decoy receptor IL-13 receptor (IL-13R) α2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13Rα2 can be regulated by IFN-γ, a type II interferon, we hypothesized that innate antiviral responses characterized by type I interferon expression can also induce IL-13Rα2 expression. OBJECTIVE: We sought to induce an innate antiviral response in primary fibroblasts using exposure to double-stranded RNA (dsRNA) and to examine the expression and function of IL-13Rα2. METHODS: Primary human fibroblasts were cultured from endobronchial biopsy specimens obtained from healthy or asthmatic volunteers and challenged with dsRNA. Upregulation of IL-13Rα2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13Rα2 protein expression was measured by using fluorescence-activated cell sorting. Eotaxin release was determined by means of ELISA. RESULTS: Direct treatment with IFN-β led to an upregulation of IL-13Rα2. Exposure to dsRNA rapidly induced IFN-β mRNA in fibroblasts, and this was followed by significant induction of IL-13Rα2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A neutralizing antibody to the IFN-α/β receptor blocked cell-surface expression of IL-13Rα2 in the presence of dsRNA. Pretreatment of fibroblasts with dsRNA led to attenuation of IL-13-stimulated eotaxin production. However, the presence of an IL-13Rα2 neutralizing antibody restored IL-13-stimulated eotaxin production in dsRNA-treated cells. CONCLUSION: IFN-β induces IL-13Rα2 expression, leading to a consequential suppression of responsiveness to IL-13. These data suggest cross-talk between TH1 and TH2 pathways and point to an immunomodulatory role for IL-13Rα2 in human bronchial fibroblasts during viral infection.
Authors: Vahe Badalyan; Robert Thompson; Kezia Addo; Lee A Borthwick; Andrew J Fisher; Tatiana Ort; Timothy G Myers; Thomas A Wynn; Thirumalai R Ramalingam Journal: J Allergy Clin Immunol Date: 2014-06-20 Impact factor: 10.793
Authors: Agnieszka Rynda-Apple; Ann Harmsen; Anfin S Erickson; Kyle Larson; Rachelle V Morton; Laura E Richert; Allen G Harmsen Journal: Eur J Immunol Date: 2014-09-01 Impact factor: 5.532
Authors: T Jartti; O Palomares; M Waris; O Tastan; R Nieminen; T Puhakka; B Rückert; A Aab; T Vuorinen; T Allander; T Vahlberg; O Ruuskanen; M Akdis; C A Akdis Journal: Allergy Date: 2014-03-29 Impact factor: 13.146