Identification, Purification, and Characterization of a Soluble Interleukin (IL)-13-binding Protein

Zhang, Jianguo; Hilton, Douglas J.; Willson, Tracy A.; McFarlane, Clare; Roberts, Bronwyn; Moritz, Robert L.; Simpson, Richard J.; Alexander, Warren S.; Metcalf, Donald; Nicola, Nicos A.

doi:10.1074/jbc.272.14.9474

Cited by 131 publications

(46 citation statements)

References 33 publications

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“…As described for the IL1 type II receptor (Bossù et al, 1995;Colotta et al, 1993), both membrane and soluble IL13R␣2 could have antagonistic activities. A natural soluble form of IL13R␣2 has been described in mouse serum and urine (Zhang et al, 1997). The protein sequence of this soluble form matches the N terminal part of the mIL13R␣2 , suggesting that it is produced by proteolytic cleavage or alternative splicing.…”

Section: Discussionmentioning

confidence: 88%

Expression of Interleukin 13 Receptor in Glioma and Renal Cell Carcinoma: IL13Rα2 as a Decoy Receptor for IL13

Bernard

Treton

Vermot-Desroches³

et al. 2001

Laboratory Investigation

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SUMMARY:Glioma and renal cell carcinoma (RCC) cells express high affinity interleukin 13 (IL13) binding sites, but only RCC cell proliferation was inhibited by IL13. Both of these two cell types are IL2-receptor ␥c chain-negative. We thus used these cell models to investigate the patterns of expression of IL13R␣1, IL13R␣2, and IL4R␣ chains and the role of IL13R␣2 in the response to IL13. Using new specific antibodies and flow cytometry, we observed a similar surface expression of IL4R␣ and IL13R␣1 chains in most RCC and glioma cells, whereas IL13R␣2 was only present on five of six glioma cell lines. In all glioma cell lines, the amount of IL13R␣2 expression was 10 to 30 times higher than that of the two other chains. Although there was no surface or intracellular expression of IL13R␣2, its mRNA was detected in three of seven RCC cell lines. The expression on RCC cells of IL13R␣2 mRNA and/or that of high-affinity IL13 binding sites is not sufficient to predict IL13R␣2 protein expression. Blocking experiments showed that IL4 and IL13 strongly inhibited RCC cell proliferation through a unique receptor composed of IL4R␣ and IL13R␣1 chains. Using RCC cells stably transfected with IL13R␣2 cDNA, we showed that the overexpression of IL13R␣2 decreased the response to IL13 but not that to IL4. Our results demonstrate that IL13R␣2 acts as a decoy receptor for IL13 and that it may exert a tight regulation of IL13 activity without impairing the IL4 response of the same cell target. (Lab Invest 2001, 81:1223-1231.

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Section: Discussionmentioning

confidence: 88%

Expression of Interleukin 13 Receptor in Glioma and Renal Cell Carcinoma: IL13Rα2 as a Decoy Receptor for IL13

Bernard

Treton

Vermot-Desroches³

et al. 2001

Laboratory Investigation

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“…A second IL-13 binding protein, IL-13R␣2, has also been identified. IL-13R␣2 shares a 37% homology with IL-13R␣1 and binds IL-13 with high affinity (50 pM) (10,(13)(14)(15). Despite this increased binding affinity, IL-13R␣2 is believed to be non-signaling and therefore may act as a "decoy" receptor.…”

Section: Il-13mentioning

confidence: 99%

“…Similarly, the expression of IL-13R␣2 in vitro does not make cells responsive to IL-13. The discovery of a soluble receptor, homologous to IL-13R␣2, in the serum and urine of mice has lent support to this regulatory role (15,16). However, this soluble protein has yet to be identified in humans.…”

Section: Il-13mentioning

confidence: 99%

Kinetic Analysis of the Interleukin-13 Receptor Complex

Andrews

Holloway²,

Puddicombe

et al. 2002

Journal of Biological Chemistry

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Interleukin (IL)-13 is a key cytokine associated with the asthmatic phenotype. It signals via its cognate receptor, a complex of IL-13 receptor ␣1 chain (IL-13R␣1) with IL-4R␣; however, a second protein, IL-13R␣2, also binds IL-13. To determine the binding contributions of the individual components of the IL-13 receptor to IL-13, we have employed surface plasmon resonance and equilibrium binding assays to investigate the ligand binding characteristics of shIL-13R␣1, shIL-13R␣2, and IL-4R␣. shIL-13R␣1 bound IL-13 with moderate affinity (K D ‫؍‬ 37.8 ؎ 1.8 nM, n ‫؍‬ 10), whereas no binding was observed for hIL-4R␣. In contrast, shIL-13R␣2 produced a high affinity interaction with IL-13 (K D ‫؍‬ 2.49 ؎ 0.94 nM n ‫؍‬ 10). IL-13R␣2 exhibited the binding characteristics of a negative regulator with a fast association rate and an exceptional slow dissociation rate. Although IL-13 interacted weakly with IL-4R␣ on its own (K D > 50 M), the presence of hIL-4R␣ significantly increased the affinity of shIL-13R␣1 for IL-13 but had no effect on the binding affinity of IL-13R␣2. Detailed kinetic analyses of the binding properties of the heteromeric complexes suggested a sequential mechanism for the binding of IL-13 to its signaling receptor, in which IL-13 first binds to IL-13R␣1 and this then recruits IL-4R␣ to stabilize a high affinity interaction.

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“…Although they share only 25% homology, IL-13 shares many functional properties with IL-4, including the up-regulation of MHC class II and CD23 Ags on monocytes (1,2). IL-13 mediates its effects via a complex receptor system that includes IL-4R␣ (IL-4R ␣-chain) and at least two other cell surface proteins, IL-13R␣1 and IL-13R␣2, which specifically bind IL-13 (3)(4)(5)(6)(7)(8). IL-13R␣1 binds IL-13 with low affinity by itself, but when paired with IL-4R␣, it binds IL-13 with high affinity and forms a functional IL-13R that signals (6).…”

Section: Reconstitution Of a Functional Human Type II Il-4/il-13mentioning

confidence: 99%

Reconstitution of a Functional Human Type II IL-4/IL-13 Receptor in Mouse B Cells: Demonstration of Species Specificity

Andrews

Rosa

Daines

et al. 2001

The Journal of Immunology

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IL-13 is a Th2-derived pleiotropic cytokine that recently was shown to be a key mediator of allergic asthma. IL-13 mediates its effects via a complex receptor system, which includes the IL-4R α-chain, IL-4Rα, and at least two other cell surface proteins, IL-13Rα1 and IL-13Rα2, which specifically bind IL-13. IL-13 has been reported to have very limited effects on mouse B cells. It was unclear whether this was due to a lack of receptor expression, a disproportionate relative expression of the receptor components, or an additional subunit requirement in B cells. To determine the requirements for IL-13 signaling in murine B cells, we examined IL-13-dependent Stat6 activation and CD23 induction in the murine B cell line, A201.1. A201.1 cells responded to murine IL-4 via the type I IL-4R, but were unresponsive to IL-13, and did not express IL-13 receptor. B220+ splenocytes also failed to signal in response to IL-13 and did not express IL-13 receptor. We transfected A201.1 cells with human IL-4Rα, IL-13Rα1, or both. Transfectants expressing either human IL-4Rα or human IL-13Rα1 alone were unable to respond or signal to IL-13. Thus, human IL-13Rα1 could not combine with the endogenous murine IL-4Rα to generate a functional IL-13R. However, cells transfected with both human IL-4Rα and IL-13Rα1 responded to IL-13. Thus, the relative lack of IL-13 responsiveness in murine B cells is due to a lack of receptor expression. Furthermore, the heterodimeric interaction between IL-4Rα and IL-13Rα1 is species specific.

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Identification, Purification, and Characterization of a Soluble Interleukin (IL)-13-binding Protein

Cited by 131 publications

References 33 publications

Expression of Interleukin 13 Receptor in Glioma and Renal Cell Carcinoma: IL13Rα2 as a Decoy Receptor for IL13

Expression of Interleukin 13 Receptor in Glioma and Renal Cell Carcinoma: IL13Rα2 as a Decoy Receptor for IL13

Kinetic Analysis of the Interleukin-13 Receptor Complex

Reconstitution of a Functional Human Type II IL-4/IL-13 Receptor in Mouse B Cells: Demonstration of Species Specificity

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