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Originally published In Press as doi:10.1074/jbc.M108109200 on January 10, 2002

J. Biol. Chem., Vol. 277, Issue 12, 10387-10393, March 22, 2002
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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 *

Michael O. Daines and Gurjit K. Khurana HersheyDagger

From the Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229

Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor alpha -1 chain (IL-13Ralpha 1) binds IL-13 with low affinity, but does not signal. However, when IL-13Ralpha 1 combines with IL-4 receptor alpha  (IL-4Ralpha ), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13Ralpha 2 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-13Ralpha 2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13Ralpha 2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN)-gamma . Up-regulation of IL-13Ralpha 2 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-13Ralpha 2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFN-gamma can regulate IL-13 responses.

* 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.

Dagger 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.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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