期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 131, 期 3, 页码 849-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.08.030
关键词
Virus; cytokine receptors; fibroblasts; type I interferon
资金
- Medical Research Council
- Synairgen
- British Lung Foundation
- MRC [G19/34, G0900453, G0501506] Funding Source: UKRI
- Asthma UK [RF06/01, 10/060] Funding Source: researchfish
- Medical Research Council [G19/34, G0900453, G0501506] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10021] Funding Source: researchfish
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) alpha 2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13R alpha 2 can be regulated by IFN-gamma, a type II interferon, we hypothesized that innate antiviral responses characterized by type I interferon expression can also induce IL-13R alpha 2 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-13R alpha 2. Methods: Primary human fibroblasts were cultured from endobronchial biopsy specimens obtained from healthy or asthmatic volunteers and challenged with dsRNA. Upregulation of IL-13R alpha 2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13R alpha 2 protein expression was measured by using fluorescence-activated cell sorting. Eotaxin release was determined by means of ELISA. Results: Direct treatment with IFN-beta led to an upregulation of IL-13R alpha 2. Exposure to dsRNA rapidly induced IFN-beta mRNA in fibroblasts, and this was followed by significant induction of IL-13R alpha 2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A neutralizing antibody to the IFN-alpha/beta receptor blocked cell-surface expression of IL-13R alpha 2 in the presence of dsRNA. Pretreatment of fibroblasts with dsRNA led to attenuation of IL-13-stimulated eotaxin production. However, the presence of an IL13R alpha 2 neutralizing antibody restored IL-13-stimulated eotaxin production in dsRNA-treated cells. Conclusion: IFN-beta induces IL-13R alpha 2 expression, leading to a consequential suppression of responsiveness to IL-13. These data suggest cross-talk between T(H)1 and T(H)2 pathways and point to an immunomodulatory role for IL-13R alpha 2 in human bronchial fibroblasts during viral infection. (J Allergy Clin Immunol 2013; 131:849-55.)
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