title: (+)-Vitisin A inhibits influenza A virus-induced RANTES production in A549 alveolar epithelial cells through interference with Akt and STAT1 phosphorylation.
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 (EC (50): 0.27 microM). However, resveratrol exhibited a much smaller effect (EC (50): 28.37 microM). H1N1 infection increased the time-dependent phosphorylation of the transcription factor STAT (1) and of Akt (a downstream effector protein of PI3K). When the PI3K-Akt pathway was blocked by wortmannin, H1N1-stimulated STAT (1) phosphorylation and RANTES production were both abrogated, demonstrating that the PI3K-Akt pathway is necessary for STAT (1) activation and RANTES production in A549 cells. Furthermore, H1N1-stimulated phosphorylation of Akt and STAT (1) 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.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Soy-Hwee
authors.initials: SH
authors.lastname: Loke
authors.forename: Ching-Chiang
authors.initials: CC
authors.lastname: Hsu
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Chiou
mesh_terms: D000230:Adenocarcinoma; D001572:Benzofurans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008175:Lung Neoplasms; D008954:Models, Biological; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000187:drug effects; D014801:Vitamin A / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D018946:Chemokine CCL5; D010636:Phenols; D050794:STAT1 Transcription Factor; D014801:Vitamin A; C412469:vitisin A; D051057:Proto-Oncogene Proteins c-akt