Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma
| Autor: | Tetsuji Yamashita, Shin-ichiro Shimazu, Xiao-Quan Mao, Ritsuko Umeshita-Suyama, Mohamad H. Sayegh, Mina Akaiwa, Julian M. Hopkin, Scott R. Brodeur, Yasuhisa Sakata, Raj K. Puri, Kazuhiko Arima, Naoto Sugawara, Yoshio Dake, Raif S. Geha, Naotaka Hamasaki, Chaker N. Adra, Kenji Izuhara, T. Shirakawa, Tadao Enomoto |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Allergy
Arginine Genotype Immunology Biology Cell Line Pathogenesis Downregulation and upregulation In vivo medicine Immunology and Allergy Humans Receptor Interleukin-13 Receptors Interleukin-13 Genetic Variation Receptors Interleukin medicine.disease Interleukin-13 Receptor alpha1 Subunit Asthma Recombinant Proteins Up-Regulation Glutamine Amino Acid Substitution Interleukin 13 |
| Zdroj: | The Journal of allergy and clinical immunology. 109(6) |
| ISSN: | 0091-6749 |
| Popis: | 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 α2 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. (J Allergy Clin Immunol 2002;109:980-7.) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect