The innate antiviral response upregulates IL-13 receptor α2 in bronchial fibroblasts.
J Allergy Clin Immunol
; 131(3): 849-55, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-23069489
ABSTRACT
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-ß led to an upregulation of IL-13Rα2. Exposure to dsRNA rapidly induced IFN-ß 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/ß 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-ß 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.
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Banco de datos:
MEDLINE
Asunto principal:
Virosis
/
Subunidad alfa2 del Receptor de Interleucina-13
/
Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido