Abstract
We examined the role of C-kinase and GTP binding protein in interferon-γ (IFN-γ) induced differentiation of human monocytic leukemia U-937 cells by using various agents that modulate both proteins. Differentiation of U-937 cells into cells with macrophage characteristics such as NBT reducing activity, Fc receptor activity, cell surface phenotype expression (CD11b, CD14), non-specific esterase activity and morphological maturation was induced by IFN-γ. The C-kinase inhibitor, H-7, did not inhibit IFN-γ-induced differentiation. The C-kinase activator, 1-oleoyl-2-acetylglycerol (OAG), did not induce differentiation of U-937 cells, but, in combination with IFN-γ, it did enhance differentiation. Thus, C-kinase may not be involved in the effectors stimulated by IFN-γ. As the number and dissociation constant of IFN-γ receptors on U-937 cells were not changed by treatment with OAG, OAG might enhance the IFN-γ-induced differentiation by modulating post-receptor events. Cholera toxin or pertussis toxin, which catalyse the transfer of ADP ribose to GTP binding proteins and lead to change of the protein functions, did not induce differentiation. However, when combined with IFN-7, cholera toxin remarkably enhanced, and pertussis toxin inhibited IFN-γ-induced differentiation. The results of intracellular cAMP concentration after treatment with IFN-γ, cholera toxin or pertussis toxin suggested that certain effectors other than adenylate cyclase might be involved in IFN-1-induced differentiation of U-937 cells.
