Planta Med 2008; 74(2): 156-162
DOI: 10.1055/s-2007-993786
Pharmacology
Original Paper
© 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

Yu-Ling Huang1 , 2 , Soy-Hwee Loke1 , Ching-Chiang Hsu3 , Wen-Fei Chiou1 , 3
  • 1National Research Institute of Chinese Medicine, Taipei, Taiwan
  • 2Center for General Education, Chang Gung Institute of Technology, Tao-Yuan, Taiwan
  • 3Institute of Life Science, Collage of Science and Engineering, National Taitung University, Taitung, Taiwan
Weitere Informationen

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

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Wen-Fei Chiou, Ph. D.

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