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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)
![](https://www.thieme-connect.de/media/plantamedica/200802/lookinside/thumbnails/10.1055-s-2007-993786-1.jpg)
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
References
- 1 Folkerts G, Busse W W, Nijkamp F P, Sorkness R, Gern J E. Virus-induced airway hyperresponsiveness and asthma. Am J Respir Crit Care Med. 1998; 157 1708-20
- 2 Matsukura S, Kokubu F, Noda H, Tokunaga H, Adachi M. Expression of IL-6, IL-8, and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virus A. J Allergy Clin Immunol. 1996; 98 1080-7
- 3 Matsukura S, Kokubu F, Kubo H, Tomita T, Tokunaga H, Kadokura M. et al . Expression of RANTES by normal airway epithelial cells after influenza virus infection. Am J Respir Cell Mol Biol. 1998; 18 255-64
- 4 Sprenger H, Meyer R G, Kaufmann A, Bussfeld D, Rischkowsky E, Gemsa D. Selective induction of monocyte and not neutrophil-attracting chemokines after influenza A virus infection. J Exp Med. 1996; 184 1191-6
- 5 Adachi M, Matsukura S, Tokunaga H, Kokubu F. Expression of cytokines on human bronchial epithelial cells induced by influenza virus A. Int Arch Allergy Immunol. 1997; 113 307-11
- 6 Mark N K, Leung C Y, Wei X Y, Shen X L, Wong R NS, Leung K N. et al . Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells. Biochem Pharmacol. 2004; 67 167-74
- 7 Melchjorsen J, Sørensen L N, Paludan S R. Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function. J Leukoc Biol. 2003; 74 331-43
- 8 Schindler C, Darnell Jr J E. Transcriptional response to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem. 1995; 64 621-51
- 9 Casola A, Burger N, Liu T, Jamaluddin M, Brasier A R, Garofalo R P. Oxidant tone regulates RANTES gene expression in airway epithelial cells infected with respiratory syncytial virus. Role in viral-induced interferon regulatory factor activation. J Biol Chem. 2001; 276 19 715-22
- 10 Darnell J E, Kerr I M, Stark G R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994; 264 1415-21
- 11 Shin Y K, Liu O, Tikoo S K, Babiuk L A, Zhou Y. Effect of the phosphatidylinositol 3-kinase/Akt pathway on influenza A virus propagation. J Gen Virol. 2007; 88 942-50
- 12 Bian Z M, Elner S G, Yoshida A, Elner V M. Differential involvement of phosphoinositide 3-kinase/Akt in human RPE MCP-1 and IL-8 expression. Invest Ophthalmol Visc Sci. 2004; 45 1887-96
- 13 Chiu N Y, Chang K H. The illustrated medicinal plants of Taiwan, Vol. 4. Taipei; SMC Publisher 1995: 147-9
- 14 Li W W, Li B G, Chen Y Z. Flexuosol A, a new tetrastilbene from Vitis flexuosa. J Nat Prod. 1998; 61 646-7
- 15 Huang Y L, Tsai W J, Shen C C, Chen C C. Resveratrol derivatives from the roots of Vitis thunbergii. . J Nat Prod. 2005; 68 217-20
- 16 Gao X, Xu Y X, Janakiraman N, Chapman R A, Gautam S C. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochem Pharmacol. 2001; 62 1299-308
- 17 Ferrero M E, Bertelli A AE, Fulgenzi A, Pellegatta F, Corsi M M, Bonfrate M. et al . Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Am J Clin Nutr. 1998; 68 1208-14
- 18 Tao H, Wu C, Zhou Y, Gong M, Zhang X, Iribarren P. et al . The grape component resveratrol interferes with the function of chemoattractant receptors on phagocytic leukocytes. Cell Mol Immunol. 2004; 1 50-6
- 19 Ko H C, Wei B L, Chiou W F. Dual regulatory effect of plant extracts of Forsythia suspense on RANTES and MCP-1 secretion in influenza A virus-infected human bronchial epithelial cells. J Ethnopharmacol. 2005; 102 418-23
- 20 Don M J, Liao J F, Lin L L, Chiou W F. Cryptotanshinone inhibits chemotactic migration in macrophages through negative regulation of PI3K signaling pathway. Br J Pharmacol. 2007; 151 38-46
- 21 Huang K S, Li R L, Wang Y H, Lin M. Three new stilbene trimers from the lianas of Gnetum hainanense. Planta Med. 2001; 67 61-4
- 22 Huang K S, Zhou S, Lin M, Wang Y H. An isorhapontigenin tetramer and a novel stilbene dimer from Gnetum hainanense. Planta Med. 2002; 68 916-20
- 23 Huang K S, Lin M, Cheng G F. Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and the conformations of the seven-membrane ring in some oligostilbenes. Phytochemistry. 2001; 58 357-62
- 24 Garcia-Alonso M, Rimbach G, Rivas-Gonzalo J C, De Pascual-Teresa S. Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A - studies in platelets, monocytes, and human endothelial cells. J Agric Food Chem. 2004; 52 3378-84
- 25 Huang K S, Lin M, Cheng G F. Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and the conformations of the seven-membrane ring in some oligostilbenes. Phytochemistry. 2001; 58 357-62
- 26 Chan M CW, Cheung C Y, Chui W H, Tsao S W, Nicholls J M, Chan Y O. et al . Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir Res. 2005; 6 135-47
- 27 Veckman V, Österlund P, Fagerlund R, Melen K, Matikainen S, Julkunen I. TNF-α and IFN-α enhance influenza-A-virus-induced chemokine gene expression in human A549 lung epithelial cells. Virology. 2006; 345 96-104
Wen-Fei Chiou, Ph. D.
Division of Basic Chinese Medical Research
National Research Institute of Chinese Medicine
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