Murine IL-4Δ2 splice variant down-regulates IL-4 activities independently of IL-4Rα binding and STAT-6 phosphorylation
| Autor: | Gil R. Diogo, Szymon Stelter, Pascal M. W. Drake, Peter Hart, Matthew J. Paul, Alastair Copland, Craig J. van Dolleweerd, Rajko Reljic, Derek C. Macallan, Adam Sparrow |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
T-Lymphocytes medicine.medical_treatment T cell Immunology Down-Regulation Nitric Oxide Immunoglobulin E Biochemistry stat Cell Line law.invention Interferon-gamma 03 medical and health sciences 0302 clinical medicine law medicine Animals Immunology and Allergy Phosphorylation Molecular Biology Interleukin 4 Cell Proliferation Mice Inbred BALB C biology Alternative splicing Hematology Molecular biology Recombinant Proteins Receptors Interleukin-4 Alternative Splicing 030104 developmental biology Cytokine medicine.anatomical_structure biology.protein Recombinant DNA Interleukin-4 STAT6 Transcription Factor 030215 immunology |
| Zdroj: | Cytokine |
| ISSN: | 1043-4666 |
| Popis: | IL-4 is a pleiotropic cytokine that is highly Th2 polarizing. The ratio of IL-4 and its splice variant IL-4Δ2 observed in human health and disease suggests a role for both isoforms. In the present study, the biological function of murine IL-4Δ2 and the potential mechanism of action were studied. We report for the first time the generation of a functional, recombinant murine IL-4Δ2 form which is suggestive of its possible biological role in this species. Recombinant murine IL-4Δ2 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-4Δ2 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. |
| Databáze: | OpenAIRE |
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