{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:23:44Z","timestamp":1790097824488,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31172325"],"award-info":[{"award-number":["31172325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31172325"],"award-info":[{"award-number":["31172325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"973 Project of China","award":["31172325"],"award-info":[{"award-number":["31172325"]}]},{"name":"973 Project of China","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}]},{"name":"973 Project of China","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}]},{"name":"973 Project of China","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}]},{"name":"973 Project of China","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}]},{"name":"973 Project of China","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}]},{"name":"New Century Excellent Talents in University","award":["31172325"],"award-info":[{"award-number":["31172325"]}]},{"name":"New Century Excellent Talents in University","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}]},{"name":"New Century Excellent Talents in University","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}]},{"name":"New Century Excellent Talents in University","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}]},{"name":"New Century Excellent Talents in University","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}]},{"name":"New Century Excellent Talents in University","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}]},{"name":"Fundamental Research Funds for the Central University","award":["31172325"],"award-info":[{"award-number":["31172325"]}]},{"name":"Fundamental Research Funds for the Central University","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}]},{"name":"Fundamental Research Funds for the Central University","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}]},{"name":"Fundamental Research Funds for the Central University","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}]},{"name":"Fundamental Research Funds for the Central University","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}]},{"name":"Fundamental Research Funds for the Central University","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}]},{"name":"Fundamental Research Funds for the Central University","award":["31172325"],"award-info":[{"award-number":["31172325"]}]},{"name":"Fundamental Research Funds for the Central University","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}]},{"name":"Fundamental Research Funds for the Central University","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}]},{"name":"Fundamental Research Funds for the Central University","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}]},{"name":"Fundamental Research Funds for the Central University","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}]},{"name":"Fundamental Research Funds for the Central University","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}]},{"name":"Transregional Collaborative Research Centre TRR 60","award":["31172325"],"award-info":[{"award-number":["31172325"]}]},{"name":"Transregional Collaborative Research Centre TRR 60","award":["81261160325"],"award-info":[{"award-number":["81261160325"]}]},{"name":"Transregional Collaborative Research Centre TRR 60","award":["2010CB530100"],"award-info":[{"award-number":["2010CB530100"]}]},{"name":"Transregional Collaborative Research Centre TRR 60","award":["NCETNCET-10-0422"],"award-info":[{"award-number":["NCETNCET-10-0422"]}]},{"name":"Transregional Collaborative Research Centre TRR 60","award":["2011PY002"],"award-info":[{"award-number":["2011PY002"]}]},{"name":"Transregional Collaborative Research Centre TRR 60","award":["2013PY051"],"award-info":[{"award-number":["2013PY051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p>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<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>\u03ba<\/mml:mi><\/mml:mrow><\/mml:math>B (NF-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>\u03ba<\/mml:mi><\/mml:mrow><\/mml:math>B). Secretion of TNF-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:mi>\u03b1<\/mml:mi><\/mml:mrow><\/mml:math>, 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.<\/jats:p>","DOI":"10.1155\/2014\/787023","type":"journal-article","created":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T17:09:20Z","timestamp":1404407360000},"page":"1-11","source":"Crossref","is-referenced-by-count":93,"title":["Roles of TLR3 and RIG-I in Mediating the Inflammatory Response in Mouse Microglia following Japanese Encephalitis Virus Infection"],"prefix":"10.1155","volume":"2014","author":[{"given":"Rong","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibo","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengbo","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.01.002"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000437"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2009.10.018"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/nm1144"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1002\/glia.1106"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.6.3916"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20474"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021761"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.05.002"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/35099560"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.02.001"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.6.3804"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-00549-7-4"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807272200"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-128"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2011.02.022"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.01.008"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2008.01.014"},{"issue":"5","key":"18","first-page":"447","volume":"52","year":"2010","journal-title":"Salud Publica de Mexico"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20928"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.01.009"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.013565-0"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00935-08"}],"container-title":["Journal of Immunology Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2014\/787023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2014\/787023.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2014\/787023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2016,7,29]],"date-time":"2016-07-29T04:48:41Z","timestamp":1469767721000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/jir\/2014\/787023\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014]]},"references-count":23,"alternative-id":["787023","787023"],"URL":"https:\/\/doi.org\/10.1155\/2014\/787023","relation":{},"ISSN":["2314-8861","2314-7156"],"issn-type":[{"value":"2314-8861","type":"print"},{"value":"2314-7156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}