The innate antiviral response upregulates IL-13 receptor ⍺2 in bronchial fibroblasts - 27/02/13
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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) ⍺2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13R⍺2 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-13R⍺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⍺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⍺2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13R⍺2 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-13R⍺2. Exposure to dsRNA rapidly induced IFN-β mRNA in fibroblasts, and this was followed by significant induction of IL-13R⍺2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A neutralizing antibody to the IFN-⍺/β receptor blocked cell-surface expression of IL-13R⍺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 IL-13R⍺2 neutralizing antibody restored IL-13–stimulated eotaxin production in dsRNA-treated cells.
Conclusion |
IFN-β induces IL-13R⍺2 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-13R⍺2 in human bronchial fibroblasts during viral infection.
Le texte complet de cet article est disponible en PDF.Key words : Virus, cytokine receptors, fibroblasts, type I interferon
Abbreviations used : dsRNA, IL-13R, Poly (I:C)
Plan
A.-L.A. is an Asthma UK Fellow and G.C.-H. has received a Medical Research Council Capacity Building PhD studentship. |
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Disclosure of potential conflict of interest: S. T. Holgate has shares in Synairgen, has received research support from the Medical Research Council and Synairgen, and is Vice President of the British Lung Foundation. D. E. Davies is cofounder of, has shares in, is a consultant for, and receives research support from Synairgen. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 3
P. 849 - mars 2013 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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