PMID- 26582142
OWN - NLM
STAT- MEDLINE
DCOM- 20160914
LR  - 20220330
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Nov 19
TI  - Dual transcriptome sequencing reveals resistance of TLR4 ligand-activated bone 
      marrow-derived macrophages to inflammation mediated by the BET inhibitor JQ1.
PG  - 16932
LID - 10.1038/srep16932 [doi]
LID - 16932
AB  - Persistent macrophage activation is associated with the expression of various 
      pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify 
      inflammatory disorders. A novel synthetic BET inhibitor, JQ1, was proven to exert 
      immunosuppressive activities in macrophages. However, a genome-wide search for 
      JQ1 molecular targets has not been undertaken. The present study aimed at 
      evaluating the anti-inflammatory function and underlying genes that are targeted 
      by JQ1 in LPS-stimulated primary bone marrow-derived macrophages (BMDMs) using 
      global transcriptomic RNA sequencing and quantitative real-time PCR. Among the 
      annotated genes, transcriptional sequencing of BMDMs that were treated with JQ1 
      revealed a selective effect on LPS-induced gene expression in which the induction 
      of cytokines/chemokines, interferon-stimulated genes, and prominent 
      (transcription factors) TFs was suppressed. Additionally, we found that JQ1 
      reduced the expression of previously unidentified genes that are important in 
      inflammation. Importantly, these inflammatory genes were not affected by JQ1 
      treatment alone. Furthermore, we confirmed that JQ1 reduced cytokines/chemokines 
      in the supernatants of LPS treated BMDMs. Moreover, the biological pathways and 
      gene ontology of the differentially expressed genes were determined in the JQ1 
      treatment of BMDMs. These unprecedented results suggest that the BET inhibitor 
      JQ1 is a candidate for the prevention or therapeutic treatment of inflammatory 
      disorders.
FAU - Das, Amitabh
AU  - Das A
AD  - Department of Bionanotechnology, Hanyang University, Seoul, 133-791, Republic of 
      Korea.
FAU - Chai, Jin Choul
AU  - Chai JC
AD  - Department of Molecular &Life Sciences, Hanyang University, Ansan, 426-791, 
      Republic of Korea.
FAU - Yang, Chul-Su
AU  - Yang CS
AD  - Department of Molecular &Life Sciences, Hanyang University, Ansan, 426-791, 
      Republic of Korea.
FAU - Lee, Young Seek
AU  - Lee YS
AD  - Department of Molecular &Life Sciences, Hanyang University, Ansan, 426-791, 
      Republic of Korea.
FAU - Das, Nando Dulal
AU  - Das ND
AD  - Epigenetics Drug Discovery Unit, Division of Structural &Synthetic Biology, RIKEN 
      Center for Life Science Technologies, 1-7-22 Suehiro-cho, Yokohama 230-0045, 
      Japan.
FAU - Jung, Kyoung Hwa
AU  - Jung KH
AD  - Institute of Natural Science &Technology, Hanyang University, Ansan, 426-791, 
      Republic of Korea.
FAU - Chai, Young Gyu
AU  - Chai YG
AD  - Department of Bionanotechnology, Hanyang University, Seoul, 133-791, Republic of 
      Korea.
AD  - Department of Molecular &Life Sciences, Hanyang University, Ansan, 426-791, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151119
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 ((+)-JQ1 compound)
RN  - 0 (Azepines)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factors)
RN  - 0 (Triazoles)
SB  - IM
MH  - Animals
MH  - Azepines/*pharmacology
MH  - Bone Marrow Cells/*pathology
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/drug effects
MH  - Inflammation/*pathology
MH  - Ligands
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects/metabolism/*pathology
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Annotation
MH  - Nuclear Proteins/*antagonists & inhibitors/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - *Sequence Analysis, RNA
MH  - Toll-Like Receptor 4/*metabolism
MH  - Transcription Factors/metabolism
MH  - Transcriptome/*genetics
MH  - Triazoles/*pharmacology
PMC - PMC4652239
EDAT- 2015/11/20 06:00
MHDA- 2016/09/15 06:00
PMCR- 2015/11/19
CRDT- 2015/11/20 06:00
PHST- 2015/04/08 00:00 [received]
PHST- 2015/10/05 00:00 [accepted]
PHST- 2015/11/20 06:00 [entrez]
PHST- 2015/11/20 06:00 [pubmed]
PHST- 2016/09/15 06:00 [medline]
PHST- 2015/11/19 00:00 [pmc-release]
AID - srep16932 [pii]
AID - 10.1038/srep16932 [doi]
PST - epublish
SO  - Sci Rep. 2015 Nov 19;5:16932. doi: 10.1038/srep16932.