Tyrosine Kinases Are Required for Interferon-y-Stlmnlated Proliferation of Trypanosoma bruce; bruce;

The tyrosine kinase activity of Trypanosoma brucei brucei upon stimulation with interferon-y (IFN-y) was investigated. IFN-y induced a rapid and strong increase of tyrosine phosphorylation of several cellular proteins that reached maximum after 5 min and was followed by a decrease to control levels after 120min. The tyrosine kinase-specific inhibitor tyrphostin A47 at a concentration of 10-6 M reduced IFN-y-induced protein phosphorylation. In vitro application of 10- 6 M tyrphostin A47 to the trypanosome cultures caused a significant reduction of [3H]thymidine uptake by IFN-y-stimulated trypanosomes. In animals, 2x 0.5 mg of tyrphostin A47 (injected intraperitoneally) caused a significant reduction of parasite growth compared with the vehicle dimethyl sulfoxide or the inactive compound tyrphostin At. In conclusion, tyrosine kinases are strongly up-regulated in IFN-y-stimulated T. b. brucei, and specific tyrosine kinase inhibitors can prevent trypanosome growth in vitro and in vivo. Microorganisms have evolved different mechanisms to es-cape host immune defenses. Some bacteria and protozoa can even use host-derived cytokines for their own growth promo-tion [1-6]. The mechanisms of cytokine-driven proliferatio