title: Roles of TLR3 and RIG-I in mediating the inflammatory response in mouse microglia following Japanese encephalitis virus infection.
abstract: Japanese encephalitis virus (JEV) infection can cause central nervous system disease with irreversible neurological damage in humans and animals. Evidence suggests that overactivation of microglia leads to greatly increased neuronal damage during JEV infection. However, the mechanism by which JEV induces the activation of microglia remains unclear. Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I) can recognize double-stranded RNA, and their downstream signaling results in production of proinflammatory mediators. In this study, we investigated the roles of TLR3 and RIG-I in the inflammatory response caused by JEV infection in the mouse microglial cell line. JEV infection induced the expression of TLR3 and RIG-I and the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK). Knockdown of TLR3 and RIG-I attenuated activation of ERK, p38MAPK, activator protein 1 (AP-1), and nuclear factor κB (NF-κB). Secretion of TNF-α, IL-6, and CCL-2, which was induced by JEV, was reduced by TLR3 and RIG-I knockdown and inhibitors of phosphorylated ERK and p38MAPK. Furthermore, viral proliferation was increased following knockdown of TLR3 and RIG-I. Our findings suggest that the signaling pathways of TLR3 and RIG-I play important roles in the JEV-induced inflammatory response of microglia.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Bibo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Cao
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D034622:RNA Interference; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D016207:Cytokines; D048049:Extracellular Signal-Regulated MAP Kinases; D018836:Inflammation Mediators; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins
references.citation: Virus Res. 2010 Jan;147(1):107-12
references.pmid: 19896511
references.citation: Int J Biochem Cell Biol. 2008;40(9):1764-74
references.pmid: 18291705
references.citation: PLoS Negl Trop Dis. 2009 Sep 29;3(9):e437
references.pmid: 19787040
references.citation: Cytokine Growth Factor Rev. 2011 Apr;22(2):63-72
references.pmid: 21466970
references.citation: Microbes Infect. 2011 Apr;13(4):312-21
references.pmid: 21238600
references.citation: Curr Opin Pharmacol. 2008 Aug;8(4):472-9
references.pmid: 18562249
references.citation: Nat Med. 2004 Dec;10(12 Suppl):S98-109
references.pmid: 15577938
references.citation: Glia. 2007 Apr 1;55(5):483-96
references.pmid: 17203475
references.citation: Neurochem Int. 2008 Jun;52(7):1310-21
references.pmid: 18325634
references.citation: J Gen Virol. 2010 Apr;91(Pt 4):1028-37
references.pmid: 20007359
references.citation: J Virol. 2008 Nov;82(21):10349-58
references.pmid: 18715906
references.citation: Neurochem Int. 2011 Jul;58(8):924-33
references.pmid: 21354239
references.citation: Virol J. 2011 Mar 20;8:128
references.pmid: 21418596
references.citation: Glia. 2001 Nov;36(2):165-79
references.pmid: 11596125
references.citation: Glia. 2010 Feb;58(3):253-63
references.pmid: 19705460
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: Salud Publica Mex. 2010 Sep-Oct;52(5):447-54
references.pmid: 21031251
references.citation: J Neuroimmunol. 2008 Mar;195(1-2):60-72
references.pmid: 18374991
references.citation: Curr Top Microbiol Immunol. 2009;336:63-81
references.pmid: 19688328
references.citation: J Immunol. 2004 Sep 15;173(6):3916-24
references.pmid: 15356140
references.citation: J Biol Chem. 2009 Apr 17;284(16):10774-82
references.pmid: 19224920
references.citation: J Immunol. 2006 Mar 15;176(6):3804-12
references.pmid: 16517751
references.citation: PLoS One. 2011;6(6):e21761
references.pmid: 21738791