Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이영식 | - |
dc.date.accessioned | 2018-02-13T04:41:14Z | - |
dc.date.available | 2018-02-13T04:41:14Z | - |
dc.date.issued | 2015-07 | - |
dc.identifier.citation | BMC GENOMICS, v. 16, Article ID. 517 | en_US |
dc.identifier.issn | 1471-2164 | - |
dc.identifier.uri | https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-015-1728-5 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/37068 | - |
dc.description.abstract | Background: Resident macrophages in the CNS microglia become activated and produce proinflammatory molecules upon encountering bacteria or viruses. TLRs are a phylogenetically conserved diverse family of sensors that drive innate immune responses following interactions with PAMPs. TLR3 and TLR4 recognize viral dsRNA Poly (I: C) and bacterial endotoxin LPS, respectively. Importantly, these receptors differ in their downstream adaptor molecules. Thus far, only a few studies have investigated the effects of TLR3 and TLR4 in macrophages. However, a genome-wide search for the effects of these TLRs has not been performed in microglia using RNA-seq. Gene expression patterns were determined for the BV-2 microglial cell line when stimulated with viral dsRNA Poly (I: C) or bacterial endotoxin LPS to identify novel transcribed genes, as well as investigate how differences in downstream signaling could influence gene expression in innate immunity. Results: Sequencing assessment and quality evaluation revealed that common and unique patterns of proinflammatory genes were significantly up-regulated in response to TLR3 and TLR4 stimulation. However, the IFN/viral response gene showed a stronger response to TLR3 stimulation than to TLR4 stimulation. Unexpectedly, TLR3 and TLR4 stimulation did not activate IFN-beta and IRF3 in BV-2 microglia. Most importantly, we observed that previously unidentified transcription factors (TFs) (i.e., IRF1, IRF7, and IRF9) and the epigenetic regulators KDM4A and DNMT3L were significantly up-regulated in both TLR3- and TLR4-stimulated microglia. We also identified 29 previously unidentified genes that are important in immune regulation. In addition, we confirmed the expressions of key inflammatory genes as well as pro-inflammatory mediators in the supernatants were significantly induced in TLR3- and TLR4-stimulated primary microglial cells. Moreover, transcriptional start sites (TSSs) and isoforms, as well as differential promoter usage, revealed a complex pattern of transcriptional and post-transcriptional gene regulation upon infection with TLR3 and TLR4. Furthermore, TF motif analysis (-950 to +50 bp of the 5' upstream promoters) revealed that the DNA sequences for NF-kappa B, IRF1, and STAT1 were significantly enriched in TLR3- and TLR4-stimulated microglia. Conclusions: These unprecedented findings not only permit a comparison of TLR3- and TLR4- stimulated genes but also identify new genes that have not been previously implicated in innate immunity. | en_US |
dc.description.sponsorship | This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (2013R1A1A3011026 to K.H.J & 2011-0030049 to Y.G.C). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | BIOMED CENTRAL LTD | en_US |
dc.subject | Gene regulation | en_US |
dc.subject | Innate immunity | en_US |
dc.subject | Toll-like receptor | en_US |
dc.subject | Microglia | en_US |
dc.subject | RNA sequencing | en_US |
dc.subject | RECEPTOR SIGNAL-TRANSDUCTION | en_US |
dc.subject | INNATE IMMUNE-RESPONSES | en_US |
dc.subject | RNA-SEQ EXPERIMENTS | en_US |
dc.subject | NF-KAPPA-B | en_US |
dc.subject | GENE-EXPRESSION | en_US |
dc.subject | IN-VIVO | en_US |
dc.subject | INFLAMMATORY | en_US |
dc.subject | DEMYELINATION | en_US |
dc.subject | ACTIVATION | en_US |
dc.subject | MACROPHAGES | en_US |
dc.subject | INHIBITORS | en_US |
dc.title | Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands | en_US |
dc.type | Article | en_US |
dc.relation.volume | 16 | - |
dc.identifier.doi | 10.1186/s12864-015-1728-5 | - |
dc.relation.page | 1-21 | - |
dc.relation.journal | BMC GENOMICS | - |
dc.contributor.googleauthor | Das, A | - |
dc.contributor.googleauthor | Chai, JC | - |
dc.contributor.googleauthor | Kim, S.H | - |
dc.contributor.googleauthor | Lee, YS | - |
dc.contributor.googleauthor | Park, KS | - |
dc.contributor.googleauthor | Jung, KH | - |
dc.contributor.googleauthor | Chai, YG | - |
dc.relation.code | 2015007838 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E] | - |
dc.sector.department | MOLECULAR AND LIFE SCIENCE | - |
dc.identifier.pid | yslee | - |
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