title: miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.
abstract: Increasing evidence confirms the involvement of virus infection and miRNA, such as miR-146a, in neuroinflammation-associated epilepsy. In the present study, we investigated the upregulation of miR-146a with RT-qPCR and in situ hybridization methods in a mice infection model of Japanese encephalitis virus (JEV) and in vitro. Subsequently we investigated the involvement of miR-146a in modulating JEV-induced neuroinflammation. It was demonstrated that JEV infection promoted miR-146a production in BALB/c mice brain and in cultured mouse microglial C8-B4 cells, along with pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, IFN-β and IFN-α. We also found that miR-146a exerted negative regulatory effects upon IL-1β, IL-6, TNF-α, IFN-β and IFN-α in C8-B4 cells. Accordingly, miR-146a downregulation with a miR-146a inhibitor promoted the upregulation of IL-1β, IL-6, TNF-α, IFN-β and IFN-α, whereas miR-146a upregulation with miR-146a mimics reduced the upregulation of these cytokines. Moreover, miR-146a exerted no regulation upon JEV growth in C8-B4 cells. In conclusion, JEV infection upregulated miR-146a and pro-inflammatory cytokine production, in mice brain and in cultured C8-B4 cells. Furthermore, miR-146a negatively regulated the production of JEV-induced pro-inflammatory cytokines, in virus growth independent fashion, identifying miR-146a as a negative feedback regulator in JEV-induced neuroinflammation, and possibly in epilepsy.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, China.
authors.forename: Minnan
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, China. juedaq_du@163.com.
authors.forename: Ganqin
authors.initials: G
authors.lastname: Du
authors.affiliation: Department of Graduate Student Section, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, China.
authors.forename: Jiegang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Du
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000254:growth & development / Q000276:immunology / Q000502:physiology; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000821:virology; D005786:Gene Expression Regulation; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D017628:Microglia / Q000276:immunology / Q000821:virology*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C577686:interleukin-6, mouse