| First Author | Grunewald SM | Year | 1997 |
| Journal | J Biol Chem | Volume | 272 |
| Issue | 3 | Pages | 1480-3 |
| PubMed ID | 8999817 | Mgi Jnum | J:38457 |
| Mgi Id | MGI:85823 | Doi | 10.1074/jbc.272.3.1480 |
| Citation | Grunewald SM, et al. (1997) A murine interleukin-4 antagonistic mutant protein completely inhibits interleukin-4-induced cell proliferation, differentiation, and signal transduction. J Biol Chem 272(3):1480-3 |
| abstractText | We characterize here a highly efficient antagonist for interleukin-4 (IL-4) in the mouse system. In this double mutant of the murine IL-4 protein, both glutamine 116 and tyrosine 119 were substituted by aspartic acid residues. This variant (QY) bound with similar affinity to the IL-4 receptor alpha subunit as wild type IL-4 without inducing cellular responses. In contrast, QY completely inhibited in a dose-dependent manner the IL-4-induced proliferation of lipopolysaccharide-stimulated murine splenic B-cells, of the murine T cell line CTLL-2, and of the murine pre-B-cell line BA/F3. QY also inhibited the IL-4-stimulated up-regulation of CD23 expression by lipopolysaccharide-stimulated murine splenic B-cells and abolished tyrosine phosphorylation of the transcription factor Stat6 and the tyrosine kinase Jak3 in IL-4-stimulated BA/F3 cells. Selective inhibition of IL-4 may be beneficial in T-helper cell type 2-dominated diseases, like type I hypersensitivity reactions or helminthic infections. The QY mutant could be an attractive tool to study in vivo the therapeutic potential of IL-4 antagonists in mouse systems. |
