| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
2 Yields Distinct Membrane and Soluble Forms1
Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229
IL-13 is a key mediator of allergic inflammation. Its diverse functions are mediated by a complex receptor system including IL-4R
, IL-13R1, and IL-13R2. IL-4R and IL-13R1 form a high-affinity signaling heterodimer. IL-13R2 binds IL-13 with high affinity and has been found to exist in membrane and soluble forms. Soluble IL-13R2 has been postulated as a critical endogenous modulator of IL-13 responses. However, the mechanism of generation for the soluble form remains unclear. We present the initial study that a mechanism for generation of the soluble form is alternative splicing and that alternative splicing yields a distinct form of soluble IL-13R2. We found that several mouse organs expressed two IL-13R2 transcripts, the 1152-bp transcript encoding the full-length protein and the 1020-bp transcript lacking exon10, which encodes the transmembrane region. Deletion of exon 10 (
Ex10) caused a frameshift resulting in a different amino acid sequence from position 327 to position 339 and early termination. Constructs encoding both splice variants were transfected into WEHI-274.1 cells. Transfectants expressing the full-length transcript had IL-13R2 on the cell surface but produced minimal soluble IL-13R2 in the supernatants. In contrast, transfectants expressing the Ex10 transcript displayed no membrane IL-13R2 but secreted high levels of soluble IL-13R2 capable of inhibiting IL-13 signaling. Both variants bound IL-13, but the Ex10 variant displayed 
2-fold increase in IL-13 binding activity. Expression of the two IL-13R2 transcripts was differentially regulated in vivo in an experimental allergic asthma model. Thus, alternatively spliced variants of IL-13R2 may have a distinct biologic function in vivo.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01AI58157 and P01HL076383 (both to G.K.K.H.).
2 Address correspondence and reprint requests to Dr. Gurjit K. Khurana Hershey, Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229. E-mail address: Gurjit.Hershey{at}cchmc.org
3 Abbreviations used in this paper: HDM, house dust mite; Ex10, deletion of exon 10.
This article has been cited by other articles:
|
|
 |
|
  A. Munitz, E. B. Brandt, M. Mingler, F. D. Finkelman, and M. E. Rothenberg Distinct roles for IL-13 and IL-4 via IL-13 receptor {alpha}1 and the type II IL-4 receptor in asthma pathogenesis PNAS, May 20, 2008; 105(20): 7240 - 7245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fichtner-Feigl, M. Terabe, A. Kitani, C. A. Young, I. Fuss, E. K. Geissler, H.-J. Schlitt, J. A. Berzofsky, and W. Strober Restoration of Tumor Immunosurveillance via Targeting of Interleukin-13 Receptor-{alpha}2 Cancer Res., May 1, 2008; 68(9): 3467 - 3475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Khodoun, C. Lewis, J.-Q. Yang, T. Orekov, C. Potter, T. Wynn, M. Mentink-Kane, G. K. Khurana Hershey, M. Wills-Karp, and F. D. Finkelman Differences in Expression, Affinity, and Function of Soluble (s)IL-4R{alpha} and sIL-13R{alpha}2 Suggest Opposite Effects on Allergic Responses J. Immunol., November 15, 2007; 179(10): 6429 - 6438. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
