A Novel Mechanism by Which Interferon-γ Can Regulate Interleukin (IL)-13 Responses
EVIDENCE FOR INTRACELLULAR STORES OF IL-13 RECEPTOR α-2 AND THEIR RAPID MOBILIZATION BY INTERFERON-γ*
- From the Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229
Abstract
Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor α-1 chain (IL-13Rα1) binds IL-13 with low affinity, but does not signal. However, when IL-13Rα1 combines with IL-4 receptor α (IL-4Rα), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13Rα2 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-13Rα2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13Rα2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN)-γ. Up-regulation of IL-13Rα2 surface expression in response to IFN-γ was rapid, did not require protein synthesis, and resulted in diminished IL-13 signaling. These results provide the first evidence that the IL-13Rα2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFN-γ can regulate IL-13 responses.
Footnotes
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↵* This work was supported in part by National Institutes of Health NICHD Grant P30HD2887.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Div. of Allergy and Immunology, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229. Tel.: 513-636-7054; Fax: 513-636-3310; E-mail: gurjit.hershey@chmcc.org.
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Published, JBC Papers in Press, January 10, 2002, DOI 10.1074/jbc.M108109200
- Abbreviations:
- IL
-
interleukin
- IL-4Rα
-
interleukin-4 receptor α chain
- IL-13Rα1
-
interleukin-13 receptor α-1 chain
- IL-13Rα2
-
interleukin-13 receptor α-2 chain
- JAK
-
Janus kinase
- Stat
-
signal transducer and activator of transcription
- IFN-γ
-
interferon-γ
- PBS
-
phosphate-buffered saline
- FBS
-
fetal bovine serum
- FITC
-
fluorescein isothiocyanate
- EMSA
-
electrophoretic mobility shift assay
- PMA
-
phorbol 12-myristate 13-acetate
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- Received August 22, 2001.
- Revision received December 9, 2001.
- The American Society for Biochemistry and Molecular Biology, Inc.
