A novel mechanism by which interferon-gamma can regulate interleukin (IL)-13 responses. Evidence for intracellular stores of IL-13 receptor alpha -2 and their rapid mobilization by interferon-gamma

Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor alpha-1 chain (IL-13Ralpha1) binds IL-13 with low affinity, but does not signal. However, when IL-13Ralpha1 combines with IL-4 receptor alpha (IL-4Ralpha), a signaling high affinity receptor complex fo...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-03, Vol.277 (12), p.10387-10393
Main Authors: Daines, Michael O, Hershey, Gurjit K Khurana
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Cells, Cultured
Dose-Response Relationship, Drug
Flow Cytometry
Gene Expression Regulation
Humans
Interferon-gamma - metabolism
interleukin 13 receptors
Interleukin-13 - metabolism
Interleukin-13 Receptor alpha1 Subunit
Interleukin-4 - metabolism
Kinetics
Microscopy, Confocal
Monocytes - metabolism
Protein Binding
Receptors, Interleukin - metabolism
Receptors, Interleukin-13
Signal Transduction
Time Factors
U937 Cells
Up-Regulation
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Summary:Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor alpha-1 chain (IL-13Ralpha1) binds IL-13 with low affinity, but does not signal. However, when IL-13Ralpha1 combines with IL-4 receptor alpha (IL-4Ralpha), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13Ralpha2 alone binds IL-13 with high affinity, but does not signal and has been postulated to be a decoy receptor. Herein, we investigated the cellular localization of IL-13Ralpha2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13Ralpha2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN)-gamma. Up-regulation of IL-13Ralpha2 surface expression in response to IFN-gamma was rapid, did not require protein synthesis, and resulted in diminished IL-13 signaling. These results provide the first evidence that the IL-13Ralpha2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFN-gamma can regulate IL-13 responses.
ISSN:0021-9258
DOI:10.1074/jbc.M108109200