Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands.

摘要: 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 TLR4 recognize viral dsRNA Poly (I:C) bacterial endotoxin LPS, respectively. Importantly, these receptors differ their downstream adaptor molecules. Thus far, only few studies have investigated effects macrophages. However, genome-wide search for has not been performed using RNA-seq. Gene expression patterns were determined BV-2 microglial cell line when stimulated LPS to identify novel transcribed genes, as well investigate how differences signaling could influence gene immunity. Sequencing assessment quality evaluation revealed common unique genes significantly up-regulated response stimulation. IFN/viral showed stronger stimulation than Unexpectedly, did activate IFN-s IRF3 microglia. Most importantly, we observed previously unidentified transcription factors (TFs) (i.e., IRF1, IRF7, IRF9) epigenetic regulators KDM4A DNMT3L both TLR3- TLR4-stimulated We also identified 29 important regulation. In addition, confirmed expressions key inflammatory pro-inflammatory mediators supernatants induced TLR3-and primary cells. Moreover, transcriptional start sites (TSSs) isoforms, differential promoter usage, complex pattern post-transcriptional regulation infection TLR4. Furthermore, TF motif analysis (-950 +50 bp 5′ upstream promoters) DNA sequences NF-κB, STAT1 enriched These unprecedented findings permit comparison but new implicated