Mechanism of action of interleukin-13 antagonist (IL-13E13K) in cells expressing various types of IL-4R

Cellular Immunology
Mitomu KioiR K Puri

Abstract

As interleukin (IL)-13 and IL-4 play a major role in various diseases including asthma, allergy, and malignancies, it is desirable to generate a molecule that blocks the effects of both cytokines. We previously generated a human IL-13 mutant (IL-13E13K), which is a powerful antagonist of IL-13, blocking the biological activities of IL-13. We now show that IL-13E13K also competitively inhibits signaling and biological activities of IL-4 through type II and partially through type III IL-4 receptor (R) system. IL-13E13K completely blocked the IL-4-induced phosphorylation of STAT6 and IL-4-dependent protein synthesis in cells expressing type II and partially type III IL-4R but not type I IL- 4R. Consistent with the inhibition of biological activities, IL-13E13K inhibited IL-4 binding to type II IL-4R-expressing cells but not to type I IL-4R-expressing cells. The inhibition efficiency of IL-4 binding by IL-13E13K was relatively lower compared to wtIL-13 even though IL-13E13K bound to IL-13Ralpha1 positive cells with a similar affinity to wtIL-13. These results indicate that Glu13 in IL-13 associates with IL-4Ralpha, and mutation to lysine decreases its binding ability to IL-4Ralpha chain. IL-13E13K binds to IL- 13Ralpha1, which is s...Continue Reading

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Citations

Oct 4, 2007·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Robert G Townley
Jun 20, 2015·Cytokine·Akiko SuzukiRaj K Puri
May 3, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·B O AbonyoA S Heiman
Oct 7, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mitomu KioiRaj K Puri
Jun 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Allison-Lynn AndrewsDonna E Davies
May 17, 2006·Technology in Cancer Research & Treatment·Mitomu KioiRaj K Puri
Apr 4, 2021·International Journal of Molecular Sciences·Jingwei ShiMarko Kornmann

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