Baicalin inhibits TLR7/MYD88 signaling pathway activation to suppress lung inflammation in mice infected with influenza A virus

Wan,Qiaofeng; Wang,Hao; Han,Xuebo; Lin,Yuan; Yang,Yanhui; Gu,Ligang; Zhao,Jiaqing; Wang,Li; Huang,Ling; Li,Yanbin; Yang,Yurong

doi:10.3892/br.2014.253

Baicalin inhibits TLR7/MYD88 signaling pathway activation to suppress lung inflammation in mice infected with influenza A virus

Authors:
- Qiaofeng Wan
- Hao Wang
- Xuebo Han
- Yuan Lin
- Yanhui Yang
- Ligang Gu
- Jiaqing Zhao
- Li Wang
- Ling Huang
- Yanbin Li
- Yurong Yang
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Affiliations: Department of Pathogen Biology and Immunology, Basic Medical Science College, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Key Laboratory of Antivirus of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
Published online on: March 14, 2014 https://doi.org/10.3892/br.2014.253
Pages: 437-441

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Abstract

The present study aimed to investigate the protective effects and underlying mechanisms of baicalin on imprinting control region mice infected with inﬂuenza A̸FM̸1̸47 (H1N1) virus. Oral administration of baicalin into mice infected with H1N1 prevented death, increased the mean time to death and inhibited lung index and lung consolidation. Subsequently, fluorescence quantitative polymerase chain reaction was used to assess the mRNA expression of toll‑like receptor 7 (TLR7) and myeloid differentiation primary response gene 88 (MYD88), and western blot analysis was used to determine the expression of phosphorylated nuclear factor κB (NF‑κB)‑P65 and c‑jun̸activator protein 1 (AP‑1). An enzyme‑linked immunosorbent assay was applied to test for the inflammatory cytokines, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β and IL‑6, in the lung tissue. The findings indicated that baicalin downregulated the mRNA expression of TLR7 and MYD88, significantly downregulated the protein expression of NF‑κB‑P65 and AP‑1 and also inhibited the secretion of TNF‑α, IL‑1β and IL‑6. In conclusion, baicalin effectively reduced the pathological damage and inflammation of the lungs by downregulating the TLR7/MYD88‑mediated signaling pathway.

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1	Romanowska M, Stefanska I, Donevski S and Brydak LB: Infections with A(H1N1)2009 influenza virus in Poland during the last pandemic: experience of the National Influenza Center. Adv Exp Med Biol. 756:271–283. 2013. View Article : Google Scholar : PubMed/NCBI
2	Wan QF, Wang H, Lin Y, et al: Effects of quercetin on CDK4 mRNA and protein expression in A549 cells infected by H1N1. Biomed Rep. 1:766–770. 2013.PubMed/NCBI
3	Le QM, Kiso M, Someya K, et al: Avian flu: isolation of drug-resistant H5N1 virus. Nature (London). 437:11082005. View Article : Google Scholar : PubMed/NCBI
4	Saito R, Li D, Suzuki H, et al: High prevalence of amantadine-resistance influenza a (H3N2) in six prefectures, Japan, in the 2005–2006 season. J Med Virol. 79:1569–1576. 2007.PubMed/NCBI
5	Sharma U, Bala M, Saini R, et al: Polysaccharide enriched immunomodulatory fractions from Tinospora cordifolia(Willd) miers ax hook. f. & Thoms. Indian J Exp Biol. 50:612–617. 2012.PubMed/NCBI
6	Evers DL, Chao CF, Wang X, et al: Human cytomegalovirus-inhibitory flavonoids: studies on antiviral activity and mechanism of action. Antiviral Res. 68:124–134. 2005. View Article : Google Scholar : PubMed/NCBI
7	Wan QF, Gu LG, Yin SJ, et al: Protection effect of baicalin on lung injury of mice infected with influenza FM1. Chin J Tradit Chin Med Pharm. 2848–2851. 2011.
8	Wan QF, Gu LG, Yin SJ, et al: Effect of baicalin on cell apoptosis FAS/FAS-L system of pneumonia mice lung tissue infected with FM1. Chin Pharmacol Bull. 27:1555–1559. 2011.
9	Kitamura K, Honda M, Yoshizaki H, et al: Baicalin, an inhibitor of HIV-1 production in vitro. Antiviral Res. 37:131–140. 1998. View Article : Google Scholar : PubMed/NCBI
10	Romero MR, Efferth T, Serrano MA, et al: Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an ‘in vitro’ replicative system. Antiviral Res. 68:75–83. 2005.PubMed/NCBI
11	Chu ZY, Chu M and Teng Y: Effect of baicalin on in vivo anti-virus. Zhongguo Zhong Yao Za Zhi. 32:2413–2415. 2007.(In Chinese).
12	Xu G, Dou J, Zhang L, et al: Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the serum. Biol Pharm Bull. 33:238–243. 2010. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Cook DN, Beck MA, Coffman TM, et al: Requirement of MIP-1α for an inflammatory response to viral infection. Science. 269:1583–1585. 1995.
15	Kawai T and Akira S: Toll-like receptor and RIG-I-like receptor signaling. Ann NY Acad Sci. 1143:1–20. 2008. View Article : Google Scholar : PubMed/NCBI
16	MacLeod H and Wetzler LM: T cell activation by TLRs: A role for TLRs in the adaptive immune response. Sci STKE. 2007:pe482007. View Article : Google Scholar : PubMed/NCBI
17	Walsh KB, Teijaro JR, Zuniga EI, et al: Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection. Cell Host Microbe. 11:643–653. 2012. View Article : Google Scholar : PubMed/NCBI
18	Rahman I, Gilmour PS, Jimenez LA, et al: Oxidative stress and TNF-α induce histone acetylation and NF-κB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol Cell Biochem. 234–235:239–248. 2002.
19	Ludwig S, Ehrhardt C, Neumeier ER, et al: Influenza virus-induced AP-1-dependent gene expression requires activation of the JNK signaling pathway. J Biol Chem. 276:10990–10998. 2001. View Article : Google Scholar
20	Adachi M, Matsukura S, Tokunaga H, et al: Expression of cytokines on human bronchial epithelial cells induced by influenza virus A. Int Arch Allergy Immunol. 113:307–311. 1997. View Article : Google Scholar : PubMed/NCBI
21	Qian C and Cao X: Regulation of toll-like receptor signaling pathways in innate immune responses. Ann NY Acad Sci. 1283:67–74. 2013. View Article : Google Scholar : PubMed/NCBI
22	Aldridge JR Jr, Moselev CE, Boltz DA, et al: TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci USA. 106:5306–5311. 2009. View Article : Google Scholar : PubMed/NCBI
23	Severa M and Fitzgerald KA: TLR-mediated activation of type I IFN during antiviral immune responses: fighting the battle to win the war. Curr Top Microbiol Immunol. 316:167–192. 2007.PubMed/NCBI
24	Tenoever BR, Ng SL, Chua MA, et al: Multiple functions of the IKK-related kinase IKKɛ in interferon-mediated antiviral immunity. Science. 315:1274–1278. 2007.PubMed/NCBI
25	Nimmerjahn F, Dudziak D, Dirmeier U, et al: Active NF-κB signaling is a prerequisite for influenza virus infection. J Gen Virol. 85:2347–2356. 2004.
26	Kumar N, Xin ZT, Liang Y, et al: NF-κB signaling differentially regulates influenza virus RNA synthesis. J Virol. 82:9880–9889. 2008.