title: Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma.
abstract: BACKGROUND
  A substantial body of evidence exists to support the pivotal role of IL-13 in the pathogenesis of bronchial asthma. We recently found that a variant of the IL13 gene (Arg110Gln) is genetically associated with bronchial asthma, which is concordant with animal experiments using IL-13 in the development of asthma.
  
  
  OBJECTIVE
  To address whether the Gln110 variant of IL13 influences IL-13 function, contributing to the pathogenesis of bronchial asthma, we studied the functional properties of the variant.
  
  
  METHODS
  We generated 2 types of recombinant IL-13 proteins, the amino acids of which at 110 were arginine or glutamine, and analyzed the binding affinities with the IL-13 receptors, as well as the stability of the proteins. We further compared the relationship between the genotype and serum levels of IL-13.
  
  
  RESULTS
  The variant showed a lower affinity with the IL-13 receptor alpha2 chain, a decoy receptor, causing less clearance. The variant also demonstrated an enhanced stability in both human and mouse plasma. We further identified that asthmatic patients homozygous for the Gln110 variant have higher serum levels of IL-13 than those without the variant.
  
  
  CONCLUSIONS
  These results suggested that the variant might act as a functional genetic factor of bronchial asthma with a unique mechanism to upregulate local and systemic IL-13 concentration in vivo.
authors.affiliation: Department of Biochemistry, Saga Medical School, Saga, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Umeshita-Suyama
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Sakata
authors.forename: Mina
authors.initials: M
authors.lastname: Akaiwa
authors.forename: Xiao-Quan
authors.initials: XQ
authors.lastname: Mao
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Dake
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Shimazu
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamashita
authors.forename: Naoto
authors.initials: N
authors.lastname: Sugawara
authors.forename: Scott
authors.initials: S
authors.lastname: Brodeur
authors.forename: Raif
authors.initials: R
authors.lastname: Geha
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
authors.forename: Mohamad H
authors.initials: MH
authors.lastname: Sayegh
authors.forename: Chaker N
authors.initials: CN
authors.lastname: Adra
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hamasaki
authors.forename: Julian M
authors.initials: JM
authors.lastname: Hopkin
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
mesh_terms: D019943:Amino Acid Substitution; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000502:physiology; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D011994:Recombinant Proteins