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Upregulation of IL-13 Concentration in Vivo by the IL13 Variant Associated With Bronchial Asthma

Upregulation of IL-13 Concentration in Vivo by the IL13 Variant Associated With Bronchial Asthma

Kazuhiko Arima, Ritsuko Umeshita-Suyama, Yasuhisa Sakata, Mina Akaiwa, Xiao-Quan Mao, Tadao Enomoto, Yoshio Dake, Shin-ichiro Shimazu, Tetsuji Yamashita, Naoto Sugawara, Scott Brodeur, Raif Geha, Raj K Puri, etc.

J Allergy Clin Immunol. 2002 Jun;109(6):980-7.

PMID: 12063528

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.
Conclusion:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248653	IL-13 Variant human			Price

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