Journal
PLANTA MEDICA
Volume 74, Issue 2, Pages 156-162Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-2007-993786
Keywords
Vitis thunbergii Sieb. & Zucc.; Vitis ficifolia Bge.; Vitaceae; influenza virus (H1N1); A549 cells; RANTES; Akt; STAT(1)
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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 mu M). However, resveratrol exhibited a much smaller effect (EC50: 28.37 mu M). H1N1 infection increased the time-dependent phosphorylation of the transcription factor STAT, and of Akt (a downstream effector protein of PI3K). When the PI3K-Akt pathway was blocked by wortmannin, H1N1-stimulated STAT, phosphorylation and RANTES production were both abrogated, demonstrating that the PI3K-Akt pathway is necessary for STAT, activation and RANTES production in A549 cells. Furthermore, H1N1-stimulated phosphorylation of Akt and STAT, 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 STAT(1)-related signal pathways.
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