Dextran sulfate inhibits IFN-gamma-induced Jak-Stat pathway in human vascular endothelial cells

Human vascular endothelial cells can be induced by IFN-gamma to express cla ss II MHC proteins. Previously, dextran sulfate was shown to selectively in hibit expression of class II MHC by preventing transcription of the gene en coding CIITA, a transactivator protein required for IFN-gamma-inducible exp ression of class II genes. In this study we characterized the effects of de xtran sulfate on the intracellular events occurring prior to CIITA activati on, Immunoprecipitation and Western blot analyses indicated that IFN-gamma- induced phosphorylation of Stat1 and Jak2 was blocked by dextran sulfate. I n addition, electron micrographs showing the large accumulation of dextran sulfate particles in the cytoplasms of endothelial cells demonstrated that Stat and Jak proteins may directly interact with dextran sulfate. Binding o f radiolabeled IFN-gamma to cells indicated that dextran sulfate may also m odulate IFN-gamma interactions with the cell surface. Thus, dextran sulfate is capable of interfering with the IFN-gamma-induced expression of class I I MHC genes at multiple sites. (C) 1999 Academic Press.