Selective DNA-binding activity of interleukin-10-stimulated STAT molecules in human monocytes.
It has been demonstrated that interferon-gamma (IFN-gamma) 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-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 Fcgamma receptor, 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 inhibited IFN-gamma-induced STAT activation without newly synthesized protein. We further demonstrated that aspirin, but not dexamethasone, suppressed IFN-gamma-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 binding to the GAS-motif sequences. This may explain the difference between IL-10 and IFN-gamma in biological activity, and the inhibitory effect of IL-10 on IFN-gamma activities.
Yamaoka
K
K
First Department of Internal Medicine, Kyushu University, Fukuoka, Japan.
Otsuka
T
T
Niiro
H
H
Nakashima
H
H
Tanaka
Y
Y
Nagano
S
S
Ogami
E
E
Niho
Y
Y
Hamasaki
N
N
Izuhara
K
K
D001241:Aspirin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects; D008565:Membrane Proteins; D008894:Milk Proteins; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013268:Stimulation, Chemical; D015534:Trans-Activators / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin