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

Eun Yong Chung, Eunmiri Roh, Jeong Ah Kwak, Heun Sik Lee, Seung Ho Lee, Chong Kil Lee, Sang Bae Han, Youngsoo Kim

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)405-414
Number of pages10
JournalJournal of Pharmacological Sciences
Volume112
Issue number4
DOIs
StatePublished - Apr 16 2010

Keywords

  • Anti-inflammation
  • Interferon (IFN)-γ
  • Macrophage
  • Signal transducer and activation of transcription-1 (STAT-1) activation
  • α-viniferin

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