Selective DNA-binding activity of interleukin-10-stimulated STAT moleculesin human monocytes

It has been demonstrated that interferon-gamma (IFN-gamma) and interleukin- 10 (IL-10) have various reverse effects on macrophages; however, the molecu lar mechanism of this difference has not been fully understood. In this stu dy, we analyzed the binding activity of IL-10- and IFN-gamma-activated STAT molecules to two kinds of GAS-motif sequences. IL-10-activated STAT1 could bind to the GAS-motif sequence in the promoter region of the Fc gamma rece ptor, but not to that in the promoter region of the COX-2 gene, whereas IFN -gamma-activated STAT1 and STAT5 could bind to both sequences. IL-10 inhibi ted IFN-gamma-induced STAT activation without newly synthesized protein. We further demonstrated that aspirin, but not dexamethasone, suppressed IFN-g amma-induced STAT activation. Taken together, these results suggest that IL -10-activated STAT1 has a specificity in binding to the GAS-motif sequences , whereas IFN-gamma-activated STAT1 and STAT5 have a broader spectrum in bi nding to the GAS-motif sequences. This may explain the difference between I L-10 and IFN-gamma in biological activity, and the inhibitory effect of IL- 10 on IFN-gamma activities.