کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5586837 | 1568713 | 2017 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Murine IL-4Î2 splice variant down-regulates IL-4 activities independently of IL-4Rα binding and STAT-6 phosphorylation
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
علوم غدد
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چکیده انگلیسی
IL-4 is a pleiotropic cytokine that is highly Th2 polarizing. The ratio of IL-4 and its splice variant IL-4Î2 observed in human health and disease suggests a role for both isoforms. In the present study, the biological function of murine IL-4Î2 and the potential mechanism of action were studied. We report for the first time the generation of a functional, recombinant murine IL-4Î2 form which is suggestive of its possible biological role in this species. Recombinant murine IL-4Î2 inhibited IL-4 mediated cellular processes in macrophages and lymphocytes. Specifically, (i) it reversed IL-4 mediated inhibition of IFN-γ induced nitric oxide release by macrophages, (ii) inhibited IL-4 mediated induction of T cell proliferation, and (iii) prevented IL-4 stimulation of IgE synthesis by B cells. However, IL-4Î2 did not compete with IL-4 for IL-4Rα binding and did not interfere with the downstream STAT-6 phosphorylation in T cells, suggesting an alternative mechanism for its antagonism of specific IL4-driven effects. These findings suggest that the mouse is a suitable experimental model for studies of the biology of IL-4 and its alternative splice variant.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cytokine - Volume 99, November 2017, Pages 154-162
Journal: Cytokine - Volume 99, November 2017, Pages 154-162
نویسندگان
Gil R. Diogo, Adam Sparrow, Matthew J. Paul, Alastair Copland, Peter J. Hart, Szymon Stelter, Craig van Dolleweerd, Pascal M.W. Drake, Derek C. Macallan, Rajko Reljic,