RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
- Title
- RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
- Author
- 이영식
- Keywords
- EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; NF-KAPPA-B; GENE-EXPRESSION; TRANSCRIPTION FACTORS; HUNTINGTONS-DISEASE; TNF-ALPHA; PATHWAY; RESPONSES; HEAT-SHOCK-PROTEIN-70
- Issue Date
- 2017-07
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v. 7, Article no. 6554
- Abstract
- Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells. Among the annotated genes, the transcriptional sequencing of microglia that were treated with GSK-J4 revealed a selective effect on LPS-induced gene expression, in which the induction of cytokines/chemokines, interferon-stimulated genes, and prominent transcription factors TFs, as well as previously unidentified genes that are important in inflammation was suppressed. Furthermore, we showed that GSK-J4 controls are important inflammatory gene targets by modulating STAT1, IRF7, and H3K27me3 levels at their promoter sites. These unprecedented results demonstrate that the histone demethylase inhibitor GSK-J4 could have therapeutic applications for neuroinflammatory diseases.
- URI
- https://www.nature.com/articles/s41598-017-06914-5https://repository.hanyang.ac.kr/handle/20.500.11754/72212
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-017-06914-5
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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