title: Effect of IL-13 receptor alpha2 levels on the biological activity of IL-13 variant R110Q.
abstract: 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) alpha 1 chain with IL-4 receptor alpha; however, a second protein, IL-13Ralpha2, 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-13Ralpha1 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-13Ralpha2 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-13Ralpha2. Eotaxin release from fibroblasts expressing low IL-13Ralpha2 levels was significantly higher in response to R110Q compared with IL-13. This was not evident in cells that had high baseline IL-13Ralpha2 levels.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Expression of R110Q and low IL-13Ralpha2 levels can result in important biological differences that may have clinical relevance in an atopic environment.
authors.affiliation: Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Allison-Lynn
authors.initials: AL
authors.lastname: Andrews
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000378:metabolism; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism*; D007700:Kinetics; D020641:Polymorphism, Single Nucleotide; D050800:STAT6 Transcription Factor / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D053663:Interleukin-13 Receptor alpha2 Subunit; D050800:STAT6 Transcription Factor