PMID- 29534174
OWN - NLM
STAT- MEDLINE
DCOM- 20190718
LR  - 20190718
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 30
IP  - 6
DP  - 2018 May 24
TI  - BATF2 activates DUSP2 gene expression and up-regulates NF-kappaB activity via 
      phospho-STAT3 dephosphorylation.
PG  - 255-265
LID - 10.1093/intimm/dxy023 [doi]
AB  - Growing evidence has revealed that the transcription factor basic leucine zipper 
      transcription factor ATF-like 2 (BATF2) has unique transcriptional activities, 
      including regulating cytokines via TLR signals in macrophages, which affect 
      mortality due to infection and cancer. On the basis of genome-wide analyses using 
      the chromatin immunoprecipitation-sequencing technique, we found that 
      dual-specificity phosphatase 2 (Dusp2) had a significantly lower acetyl-histone 
      status in Batf2-/- bone marrow-derived macrophages (BMDMs) compared with 
      wild-type (WT) BMDMs. The phosphatase DUSP2 has been reported to play a critical 
      role in inflammatory responses. Therefore, we evaluated the BATF2 transcriptional 
      activities on the Dusp2 promoter. We found that the DUSP2 and IL-12 p40 
      expression levels were significantly lower in Batf2-/- BMDMs than in WT controls 
      following their stimulation with TLR7 ligands. Further in vitro studies revealed 
      that phospho-STAT3 was up-regulated and NF-kappaB p50/p65 were down-regulated in 
      Batf2-/- BMDMs compared with their levels in WT controls. Additionally, Th1 
      immunity was impaired in Batf2-/- mice following their stimulation with TLR7 
      ligands. We also found that BATF2 interacts with NF-kappaB p65 and promotes DUSP2 
      expression through the NF-kappaB-binding site in the Dusp2 promoter at -203 to -121. 
      Collectively, our findings suggest that BATF2 activates DUSP2 gene expression and 
      up-regulates NF-kappaB activity via phospho-STAT3 dephosphorylation.
FAU - Kanemaru, Hisashi
AU  - Kanemaru H
AD  - Department of Host Defense, Research Institute for Microbial Diseases (RIMD), 
      Osaka University, Suita, Osaka, Japan.
FAU - Yamane, Fumihiro
AU  - Yamane F
AD  - Department of Host Defense, Research Institute for Microbial Diseases (RIMD), 
      Osaka University, Suita, Osaka, Japan.
FAU - Tanaka, Hiroki
AU  - Tanaka H
AD  - Department of Host Defense, Research Institute for Microbial Diseases (RIMD), 
      Osaka University, Suita, Osaka, Japan.
AD  - Laboratory of Host Defense, Immunology Frontier Research Center (IFReC), Osaka 
      University, Suita, Osaka, Japan.
FAU - Maeda, Kazuhiko
AU  - Maeda K
AD  - Department of Host Defense, Research Institute for Microbial Diseases (RIMD), 
      Osaka University, Suita, Osaka, Japan.
AD  - Laboratory of Host Defense, Immunology Frontier Research Center (IFReC), Osaka 
      University, Suita, Osaka, Japan.
FAU - Satoh, Takashi
AU  - Satoh T
AD  - Department of Host Defense, Research Institute for Microbial Diseases (RIMD), 
      Osaka University, Suita, Osaka, Japan.
AD  - Laboratory of Host Defense, Immunology Frontier Research Center (IFReC), Osaka 
      University, Suita, Osaka, Japan.
FAU - Akira, Shizuo
AU  - Akira S
AD  - Department of Host Defense, Research Institute for Microbial Diseases (RIMD), 
      Osaka University, Suita, Osaka, Japan.
AD  - Laboratory of Host Defense, Immunology Frontier Research Center (IFReC), Osaka 
      University, Suita, Osaka, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (BATF2 protein, mouse)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 2)
RN  - EC 3.1.3.48 (Dusp2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Basic-Leucine Zipper Transcription Factors/deficiency/*metabolism
MH  - Dual Specificity Phosphatase 2/*genetics/metabolism
MH  - Gene Expression Profiling
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism
MH  - Phosphorylation
MH  - RAW 264.7 Cells
MH  - STAT3 Transcription Factor/*metabolism
MH  - *Up-Regulation
EDAT- 2018/03/14 06:00
MHDA- 2019/07/19 06:00
CRDT- 2018/03/14 06:00
PHST- 2017/11/20 00:00 [received]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/03/14 06:00 [pubmed]
PHST- 2019/07/19 06:00 [medline]
PHST- 2018/03/14 06:00 [entrez]
AID - 4925475 [pii]
AID - 10.1093/intimm/dxy023 [doi]
PST - ppublish
SO  - Int Immunol. 2018 May 24;30(6):255-265. doi: 10.1093/intimm/dxy023.