It has been demonstrated that interferon-γ (IFN-γ) and interleukin-10 (IL-10) have various reverse effects on macrophages; however, the molecular mechanism of this difference has not been fully understood. In this study, we analyzed the binding activity of IL-10- and IFN-γ-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 Fcγ receptor, but not to that in the promoter region of the COX-2 gene, whereas IFN-γ-activated STAT1 and STATS could bind to both sequences. IL-10 inhibited IFN-γ-induced STAT activation without newly synthesized protein. We further demonstrated that aspirin, but not dexamethasone, suppressed IFN-γ-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-γ-activated STAT1 and STAT5 have a broader spectrum in binding to the GAS-motif sequences. This may explain the difference between IL-10 and IFN-γ in biological activity, and the inhibitory effect of IL-10 on IFN-γ activities.
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