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DOI: 10.1055/s-2007-993786
© Georg Thieme Verlag KG Stuttgart · New York
(+)-Vitisin A Inhibits Influenza A Virus-Induced RANTES Production in A549 Alveolar Epithelial Cells through Interference with Akt and STAT1 Phosphorylation
Publikationsverlauf
Received: August 3, 2007
Revised: November 19, 2007
Accepted: November 27, 2007
Publikationsdatum:
31. Januar 2008 (online)


Abstract
Airway epithelial cells are the initial sites of influenza virus infection. They participate in the airway inflammatory response by expressing various chemokines such as regulated on activation, normal T cell expressed and secreted (RANTES). In the present investigation, the effects of five stilbenes previously isolated from the roots of Vitis thunbergii on RANTES produced by influenza A virus (H1N1)-infected A549 alveolar epithelial cells were studied. We identified (+)-vitisin A, a tetramer of resveratrol, as a potent agent that inhibits RANTES secretion (EC50: 0.27 μM). However, resveratrol exhibited a much smaller effect (EC50: 28.37 μM). H1N1 infection increased the time-dependent phosphorylation of the transcription factor STAT1 and of Akt (a downstream effector protein of PI3K). When the PI3K-Akt pathway was blocked by wortmannin, H1N1-stimulated STAT1 phosphorylation and RANTES production were both abrogated, demonstrating that the PI3K-Akt pathway is necessary for STAT1 activation and RANTES production in A549 cells. Furthermore, H1N1-stimulated phosphorylation of Akt and STAT1 were also significantly attenuated by (+)-vitisin A. These results suggested that (+)-vitisin A might be a potent anti-inflammatory agent that inhibits influenza A virus-induced RANTES production by interfering with Akt- and STAT1-related signal pathways.
Abbreviations
CCL:CC chemokine ligand
ERK:extracellular signal-regulated kinase
IFN-γ:interferon-γ
Jak:Janus kinase
MCP-1:monocyte chemoattractant protein-1
NF-κB:nuclear factor-κB
NP-40:nonylphenoxy(polyethoxy)ethanol
Pl3K-Akt:phosphatidylinositol-3-kinase (Pl3K)-Akt
PMSF:phenylmethylsulfonyl fluoride
RANTES:regulated on activation, normal T cell expressed and secreted
SDS:lauryl sulfate sodium salt
STAT:signal transducer and activator of transcription
Key words
Vitis thunbergii Sieb. & Zucc. - Vitis ficifolia Bge. - Vitaceae - influenza virus (H1N1) - A549 cells - RANTES - Akt - STAT1