α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages

• Published in: Journal of Pharmacological Sciences 2010, Vol.112(4), pp.405-414
• Main Authors: Chung, Eun Yong, Roh, Eunmiri, Kwak, Jeong-Ah, Lee, Heun-Sik, Lee, Seung Ho, Lee, Chong-Kil, Han, Sang-Bae, Kim, Youngsoo
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammation; Base Sequence; Benzofurans - pharmacology; Blotting, Western; Cell Line; Chemokines - metabolism; DNA Primers; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Inflammation - genetics; interferon (IFN)-γ; Interferon-gamma - pharmacology; macrophage; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Protein Kinases - metabolism; Reverse Transcriptase Polymerase Chain Reaction; signal transducer and activation of transcription-1 (STAT-1) activation; STAT1 Transcription Factor - physiology; α-viniferin
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.09247FP

α-Viniferin, an oligostilbene of trimeric resveratrol, has been reported to have antiinflammatory 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 transducer 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 extracellular 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 inflammatory 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 antiinflammatory mechanism of α-viniferin, down-regulating STAT-1–inducible inflammatory genes via inhibiting ERK-mediated STAT-1 activation in IFN-γ–stimulated macrophages.