The Signal Pathways of Immune Inflammation Mediated by the Tlr3/Nf-Kappab and Activator Protein-1 in Cells Infected with Influenza A Virus Antagonized by Baicalin

Abstract:

Baicalin has better anti-inflammatory function, antioxidant function and antiviral activity, but the mechanism of the antiinfluenza viral activity of baicalin has not been revealed.Toll-like Receptor 3 and the signal pathways mediated by TLR3 were affected and controlled by the infections with influenza A virus. We report here the significant activity and part mechanism of baicalin against H3N2 influenza A viruses. Baicalin could well protect the damages of cells caused by influenza A virus, it also could effectively inhibit the production of CPE in cells caused by influenza A virus and the inhibition of cells growth. The mechanism of antiinfluenza virus infection of baicalin may be related with the following aspects: to decrease the transcriptional activity of the oxidative stress sensitive transcription factor NF-kappaB and AP-1 by moderately decrease the higher expression level of TLR3 mRNA and the higher expression level of protein; and to further inhibit the mRNA expression of the downstream target genes IL-1β, IL-8, RANTES and IFN-β thereby alleviate the inflammatory injuries and restore the stability and balance of immune function in vivro.

• Periodical: Advanced Materials Research (Volume 345)
• Pages: 201-209
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.345.201
• Online since: September 2011
• Authors: Chun Jing Zhang, Hai Tao Yu
• Keywords: Activating Protein-1, Baicalin, Immune and Inflammatory Cytokines, Influenza A Virus, Nuclear Factor-Kappa B, Toll-Like Receptor 3

References

[1] H. -B. Shu, Antiviral Innate Immunity, Science Press, 2009, pp.13-39, 79-105.

[2] L. Sompayrac, How Pathogenic Viruses Work, Authorized translation from the English language edition published by Johns and Bartlett Publishers Inc, (2002).

[3] N. -K. Maka, C. -Y. Leunga, X. -Y. Wei, et al, Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells, Biochemical Pharmacology, 2004, vol. 67, pp.167-174.

DOI: 10.1016/j.bcp.2003.08.020

[4] J. -P. Wang, G. -N. Bowen, C. Padden, et al, Toll-like receptor-mediated activation of neutrophils by influenza A virus, Blood, 2008, vol. 112, no. 5, p.2028-(2034).

DOI: 10.1182/blood-2008-01-132860

[5] I. Rahman, P. -S. Gilmour, L. -A. Jimenez, et al, Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation, Mol Cell Biochem, 2002, pp.234-235.

DOI: 10.1007/978-1-4615-1087-1_28

[6] I. Rahman, Oxidation stress in pathogenesis of chronic obstructive pulmonary diease: cellular and molecular mechaniss, Cell Biochem Biophys, 2005 vol. 43, pp.167-188.

[7] S. Ludwig, C. Ehrhardt, E. -R. Neumeier, et al, Influenza virus-induced AP-1-dependent gene expression requires activation of the JNK signaling pathway, J Biol Chem, 2001, vol. 276, pp.10990-10998.

DOI: 10.1074/jbc.m009902200

[8] L. Liu, L. -K. Gong, H. Wang, et al, Baicalin inhibits macrophage activation by lipopolysaccharide and protects mice from endotoxin shock, Biochemical pharmacology, 2008 vol. 75, pp.914-922.

DOI: 10.1016/j.bcp.2007.10.009

[9] Pharmacopoeia Committee of Ministry of Health of People's Republic of China, The Chinese Pharmacopoeia, Beijing: Chemical Industry Press, 2005, pp.211-212.

[10] T. -H. Zhao, S. -P. Chen, H. -S. Yang, et al, Studies on the Antiviral Function of the Active Part of Scutellaria Leaves and Stems, China Pharmaceutical University Transaction, 2006 vol. 37, no. 6, pp.544-547.

[11] C. -C. Chen, M. -P. Chow, W. -C. Huang, et al, Flavonoids Inhibit Tumor Necrosis Factor-α-Induced Up-Regulation of Intercellular Adhesion Molecule-1 (ICAM-1) in Respiratory Epithelial Cells through Activator Protein-1 and Nuclear Factor-κB: Structure-Activity Relationships, Mol Pharmacol, 2004 vol. 66, no. 3, p.683.

[12] K. Aaby, E. Hvattum, G. Skrede, Analysis of flavonoids and other phenolic compounds using high-performance liquid chromatography with coulometric array detection: relationship to antioxidant activity, J Agric Food Chem, 2004 vol. 15, p.4595.

DOI: 10.1021/jf0352879

[13] T. Nagai, R. Moriuchi, Y. Suzuki, et a1, Mode of action of the anti -1nfluenza virus activity of plant flavonold, 5, 7, 4'-trihydroxy-8-methoxyflavone , from the roots of Scutellaria baicalensls, Antiviral Res, 1995 vol. 26, no. 1, p.11.

DOI: 10.1016/0166-3542(94)00062-d

[14] Y. Cheng, J. Ping, H. -D. Xu, et a1, Synergistic effect of a novel oxymatrine-baicalin combination against hepatitis B virus replication, alpha smooth muscle actin expression and type I collagen synthesis in vitro, World J Gastroenterol, 2006, vol. 12, no. 32, pp.5153-5159.

[15] S. -YLyu, J. -Y. Rhim, W. -B. Park, Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro, Arch Pharm Res, 2005, vol. 28, no. 11, pp.1293-1301.

DOI: 10.1007/bf02978215

[16] Z. -Y. Chu, M. Chu, Y. Teng, The in vivo Anti-influenza A virus Function of Baicalin, Chin J Chin Mater Med, 2007, vol. 32, no. 22, pp.2413-2415.

[17] G. Xu, J. Dou, L. Zhang, et a1, Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the serum, Biol Pharm Bull, 2010, vol. 33, no. 2, pp.238-243.

DOI: 10.1248/bpb.33.238

[18] C. -J. Zhang, H. -T. Yu, Antagonism of Geniposide on Toll-like receptor7 /Nuclear Factor-κB signaling pathways in cells With influenza A virus infection, Chin J Microbiol Immunol, 2010, vol. 30, no. 8, pp.749-754.

[19] C. -J. Zhang, L. -G. Gu, X. -Y. Niu, et al, Effect and Mechanism of Ginsenoside Rg1and Rb1 on Influenza A Virus Infection, Chin J Microbiol Immunol, 2009, vol. 29, no. 10, pp.894-898.

[20] Q. -DTrinh, Y. Izumi, S. Komine-Aizawa, et al, H3N2 Influenza A Virus Replicates in Immortalized Human First Trimester Trophoblast Cell Lines and Induces Their Rapid Apoptosis, American Journal of Reproductive Immunology, 2009, vol. 62, pp.139-146.

DOI: 10.1111/j.1600-0897.2009.00723.x

[21] M. Sumikoshi, K. Hashimoto, Y. Kawasaki, et al, Human Influenza Virus Infection and Apoptosis Induction in Human Vascular Endothelial Cells, Journal of Medical Virology, 2008, vol. 80, pp.1072-1078.

DOI: 10.1002/jmv.21185

[22] S. Herold, M. Steinmueller, W. Wulffen, et al, Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis inducing ligand, JExp Med, 2008, vol. 205, no. 13, pp.3065-3077.

DOI: 10.1084/jem.20080201

[23] L. Chaperot, A. Blum, O. Manches, et al, Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells, JImmunol, 2006, vol. 176, pp.248-255.

DOI: 10.4049/jimmunol.176.1.248

[24] E. Ishikawa, M. Nakazawa, M. Yoshinari, Role of tumor necrosis factor-related apoptosis-inducing ligand in immune response to influenza virus infection in mice, J Virol, 2005, vol. 79, no. 12, pp.7658-7663.

DOI: 10.1128/jvi.79.12.7658-7663.2005

[25] S. Ludwig, S. Pleschka, O. Planz, et al, Ringing the alarm bells: signalling and apoptosis in influenza virus infected cells, Cell Microbiol, 2006, vol. 8, pp.375-386.

DOI: 10.1111/j.1462-5822.2005.00678.x

[26] I. Julkunen, T. Sareneva, J. Pirhonen, et al, Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression, Cytokine Growth Factor Rev, 2001, vol. 12, pp.171-180.

DOI: 10.1016/s1359-6101(00)00026-5

[27] A. Kaufmann, R. Salentin, R. -G. Meyer, et al, Defense against Influenza A Virus Infection: Essential Role of the Chemokine System, Immunobiol, 2001, vol. 204, pp.603-613.

DOI: 10.1078/0171-2985-00099

[28] D. -S. Bischoff, J. -H. Zhu, N. -S. Makhijani, et al, Acidic pH stimulates the production of the angiogenic CXC chemokine, CXCL8 (interleukin-8), in human adultmesenchymal stem cells via the extracellular signal-regulated kinase, p.38.

DOI: 10.1002/jcb.21714

[29] M. -K. Rasmussen, L. Iversen, C. Johansen, et al, IL-8 and p.53 are inversely regulated through JNK, p.38 and NF - kappaB p.65 in HepG2 cells during an inflammatory response, Inf lamm Res, 2008, vol. 57, no. 7, pp.329-339.

DOI: 10.1007/s00011-007-7220-1

[30] E. -Y. Choi, Z. -Y. Park, E. -J. Choi, et al, Transcrip tional regulation of IL-8 by iron chelator in human epithelial cells is independent from NF-kappaB but involves ERK1/2-and p.38.

[31] L. Guillot, R. Le Goffic, S. Bloch, et al, Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus, J Biol Chem, 2005, vol. 280, no. 7, pp.5571-5580.

DOI: 10.1074/jbc.m410592200

[32] B. -D. Rudd, E. Burstein, C. -S. Duckett, et al, Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine Expression, Journal of Virology, 2005, vol. 79, no. 6, pp.3350-3357.

DOI: 10.1128/jvi.79.6.3350-3357.2005

[33] R. -L. Goffic, V. Balloy, M. Lagranderie, et al, Detrimental contribution of the Toll-like receptor(TLR)3 to influenza A virus-induced acute pneumonia, PLoS Pathogens, 2006, vol. 2, no. 6, pp.526-535.

DOI: 10.1371/journal.ppat.0020053