α-Viniferin suppresses the signal transducer and activation of transcription-1 (stat-1)-inducible inflammatory genes in interferon-γ-stimulated macrophages

Α-viniferin,an oligostilbene of trimeric resveratrol,has been reported to have anti-inflammatory potential in carrageenin-induced paw edema or adjuvant-induced arthritis in animal models. however,little is known about the molecular basis. in this study,α-viniferin at 3 - 10 μm dose-dependently inhibited interferon (ifn)-γ-induced ser727 phosphorylation of the signal trans-ducer and activation of transcription-1 (stat-1),a pivotal transcription factor controlling ifn-γ-targeted genes,in raw 264.7 macrophages,and also ifn-γ-induced activation of the extracel-lular signal-regulated kinase (erk)-1,a protein kinase upstream of the ser727 phosphorylation of stat-1. however,α-viniferin,only at a higher concentration of 10 μm,inhibited janus kinase 2-mediated tyr701 phosphorylation of stat-1 in the cells. to understand stat-1-dependent in-flammatory responses,we quantified nitric oxide (no) or chemokines. α-viniferin at 3 - 10 μm dose-dependently inhibited ifn-γ-induced production of no,ifn-γ-inducible protein-10 (ip-10),or the monokine induced by ifn-γ (mig) in raw 264.7 cells and also that of no in primary macrophages-derived from c57bl/6 mice. furthermore,α-viniferin diminished ifn-γ-induced protein levels of inducible no synthase (inos),attenuated mrna levels of inos,ip-10,or mig as well as inhibited promoter activity of the inos gene. in conclusion,this study proposes an anti-inflammatory mechanism of α-viniferin,down-regulating stat-1-inducible inflammatory genes via inhibiting erk-mediated stat-1 activation in ifn-γ-stimulated macrophages. © 2010 the japanese pharmacological society.