eCAM Advance Access published online on July 10, 2009
eCAM, doi:10.1093/ecam/nep066
8-Prenylkaempferol Suppresses Influenza A Virus-Induced RANTES Production in A549 Cells via Blocking PI3K-Mediated Transcriptional Activation of NF-
B and IRF3
1National Research Institute of Chinese Medicine, Taipei,2Institute of Life Science, Collage of Science and Engineering, National Taitung University, Taitung and 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
8-Prenylkaempferol (8-PK) is a prenylflavonoid isolated from Sophora flavescens, a Chinese herb with antiviral and anti-inflammatory properties. In this study, we investigated its effect on regulated activation, normal T cell expressed and secreted (RANTES) secretion by influenza A virus (H1N1)-infected A549 alveolar epithelial cells. Cell inoculation with H1N1 evoked a significant induction in RANTES accumulation accompanied with time-related increase in nuclear translocation of nuclear factor-
B (NF-B) and interferon regulatory factor 3 (IRF-3), but showed no effect on c-Jun phosphorylation. 8-PK could significantly inhibit not only RANTES production but also NF-B and IRF-3 nuclear translocation. We had proved that both NF-B and IRF-3 participated in H1N1-induced RANTES production since NF-B inhibitor pyrrolidinedithio carbamate (PDTC) and IRF-3 siRNA attenuated significantly RANTES accumulation. H1N1 inoculation also increased PI3K activity as well as Akt phosphorylation and such responsiveness were attenuated by 8-PK. In the presence of wortmannin, nuclear translocation of NF-B and IRF3 as well as RANTES production by H1N1 infection were all reversed, demonstrating that PI3K–Akt pathway is essential for NF-B- and IRF-3-mediated RANTES production in A549 cells. Furthermore, 8-PK but not wortmannin, prevented effectively H1N1-evoked IB degradation. In conclusion, 8-PK might be an anti-inflammatory agent for suppressing influenza A virus-induced RANTES production acts by blocking PI3K-mediated transcriptional activation of NF-B and IRF-3 and in part by interfering with IB degradation which subsequently decreases NF-B translocation.
Keywords: Akt – H1N1 – IRF-3 – NF-B – PI3K – 8-prenylkaempferol – RANTES – Sophora flavescens
For reprints and all correspondence: Wen-Fei Chiou, Ph.D., Division of Basic Chinese Medical Research, National Research Institute of Chinese Medicine, No. 155-1, Sec. 2, Li-Nung St, Shipai, Taipei 112, Taiwan, ROC. Tel: +886-2-2820199 (4481); Fax: +886-2-28264343; E-mail: wfchiou{at}cma23.nricm.edu.tw
Received July 10, 2008; accepted June 3, 2009