Effect of IL-13 receptor α2 levels on the biological activity of IL-13 variant R110Q

Andrews, Allison-Lynn; Bucchieri, Fabio; Arima, Kazuhiko; Izuhara, Kenji; Holgate, Stephen T.; Davies, Donna E.; Holloway, John W.

doi:10.1016/j.jaci.2007.04.026

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 120, Issue 1 , Pages 91-97, July 2007

Effect of IL-13 receptor α2 levels on the biological activity of IL-13 variant R110Q

Allison-Lynn Andrews, PhD
- From the Infection, Inflammation and Repair Division
Fabio Bucchieri, MD
- Department of Experimental Medicine, Human Anatomy Section, University of Palermo
Kazuhiko Arima, MD
- Department of Biomolecular Sciences, Saga Medical School
Kenji Izuhara, MD
- Department of Biomolecular Sciences, Saga Medical School
Stephen T. Holgate, DSc
- From the Infection, Inflammation and Repair Division
Donna E. Davies, PhD
- From the Infection, Inflammation and Repair Division
John W. Holloway, PhD
- From the Infection, Inflammation and Repair Division
- Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital
- Reprint requests: John W. Holloway, PhD, MP810, Level F, South Block, Southampton General Hospital, Southampton SO16 6YD, United Kingdom.

Received 17 July 2006; received in revised form 16 April 2007; accepted 18 April 2007. published online 13 June 2007.

Southampton, United Kingdom, Palermo, Italy, and Saga, Japan

Background

IL-13 is a key cytokine associated with the asthmatic phenotype. IL-13 signals via its cognate receptor, a complex of IL-13 receptor (IL-13R) α 1 chain with IL-4 receptor α; however, a second protein, IL-13Rα2, also binds IL-13. Recently a polymorphic variant of IL-13 (R110Q) has been shown to be associated with atopy.

Objective

To investigate the binding properties of this IL-13 variant to its cognate receptors.

Methods

We used surface plasmon resonance to measure the binding kinetics of R110Q to its receptors. Primary human fibroblasts were grown from endobronchial biopsies obtained from volunteers. Receptor levels were measured by fluorescence-activated cell sorting.

Results

There was no significant difference in the binding of R110Q with soluble human IL-13Rα1 compared with IL-13 (32 ± 5 nmol/L and 36 ± 7 nmol/L, respectively; P = .625). However, a small but significant difference was observed in the binding of R110Q to soluble human IL-13Rα2 compared with IL-13 (840 ± 87 pmol/L and 1.1 ± .05 nmol/L, respectively; P = .04). We observed that primary human lung fibroblasts expressed different levels of IL-13Rα2. Eotaxin release from fibroblasts expressing low IL-13Rα2 levels was significantly higher in response to R110Q compared with IL-13. This was not evident in cells that had high baseline IL-13Rα2 levels.

Conclusion

These results suggest that relatively small changes in functional properties of a ligand combined with variation in receptor levels in vivo can result in significant differences in responsiveness.