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.