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

Title
alpha-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)-Inducible Inflammatory Genes in Interferon-gamma-Stimulated Macrophages
Author(s)
이승호정은영[정은영]노은미리[노은미리]곽정아[곽정아]이현식[이현식]이종길[이종길]한상배[한상배]김영수[김영수]
Keywords
PROTEIN-TYROSINE KINASES; NITRIC-OXIDE SYNTHASE; CARCINOMA A431 CELLS; IFN-GAMMA; SERINE PHOSPHORYLATION; JAK-STAT; KAPPA-B; TARGETED DISRUPTION; RESPONSE ELEMENT; INNATE IMMUNITY
Issue Date
201003
Publisher
JAPANESE PHARMACOLOGICAL SOC
Citation
JOURNAL OF PHARMACOLOGICAL SCIENCES, v.112, no.4, pp.405 - 414
Abstract
alpha-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, alpha-viniferin at 3 - 10 mu M dose-dependently inhibited interferon (IFN)-gamma induced Ser(727) phosphorylation of the signal transducer and activation of transcription-1 (STAT-1), a pivotal transcription factor controlling IFN-gamma targeted genes, in RAW 264.7 macrophages, and also IFN-gamma-induced activation of the extracellular signal-regulated kinase (ERK)-1, a protein kinase upstream of the Ser(727) phosphorylation of STAT-1. However, alpha-viniferin, only at a higher concentration of 10 mu M, inhibited Janus kinase 2-mediated Tyr(701) phosphorylation of STAT-1 in the cells. To understand STAT-1 dependent inflammatory responses, we quantified nitric oxide (NO) or chemokines. alpha-Viniferin at 3-10 mu M dose-dependently inhibited IFN-gamma induced production of NO, IFN-gamma inducible protein-10 (IP-10), or the monokine induced by IFN-gamma (MIG) in RAW 264.7 cells and also that of NO in primarymacrophages-derived from C57BL/6 mice. Furthermore, alpha-viniferin diminished IFN-gamma-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 alpha-viniferin, down-regulating STAT-1-inducible inflammatory genes via inhibiting ERK-mediated STAT-1 activation in IFN-gamma stimulated macrophages.
URI
http://hdl.handle.net/YU.REPOSITORY/22787http://dx.doi.org/10.1254/jphs.09247FP
ISSN
1347-8613
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약학대학 > 약학부 > Articles
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