Interleukin-13 induces rapid tyrosine phosphorylation and activation of Raf-1 kinase in human monocytic progenitor cell line U937.

IL-13 is a pleiotropic cytokine produced by Th0, Th1-like, and CD8 T cells in response to antigen stimulation. Its biological effects include suppression of cytotoxic activity of monocytes/macrophages and suppression of pro-inflammatory cytokine production. However, the mechanism of IL-13 remains unknown. In this study we investigated the effects of rhIL-13 on tyrosine phosphorylation in U937 monocytic progenitor cells by immunoblotting and immunocomplex kinase assays. We demonstrate that rhIL-13 stimulates dose-dependent tyrosine phosphorylation of several proteins of Mr. 93, 80, 74, 49.5, 42, 30, 22 and 18 kDa within 30 sec. The effect of IL-13 was blocked by the tyrosine kinase inhibitor erbstatin. Furthermore, IL-13 induces tyrosine phosphorylation and rapid activation of raf-1 kinase. These findings provide the first evidence that the mechanism of IL-13 involves rapid tryrosine phosphorylation and activation of raf-1 serine/threonine kinase.