PMID- 24023826
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 9
DP  - 2013
TI  - Transcription of Tnfaip3 is regulated by NF-kappaB and p38 via C/EBPbeta in activated 
      macrophages.
PG  - e73153
LID - 10.1371/journal.pone.0073153 [doi]
LID - e73153
AB  - Macrophages play a pivotal role in the immune system through recognition and 
      elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages 
      interact with microbial substances and initiate signal transduction through 
      intracellular adapters. TLR4, which recognizes the lipopolysaccharides (LPS) on 
      Gram-positive and Gram-negative bacteria, triggers downstream signaling mediators 
      and eventually activates IkappaB kinase (IKK) complex and mitogen-activated protein 
      kinases (MAPKs) such as p38. Previous reports revealed that, in addition to 
      NF-kappaB, a core transcription factor of the innate immune response, the induction 
      of some LPS-induced genes in macrophages required another transcription factor 
      whose activity depends on p38. However, these additional transcription factors 
      remain to be identified. In order to identify p38-activated transcription factors 
      that cooperate with NF-kappaB in response to LPS stimulation, microarrays were used 
      to identify genes regulated by both NF-kappaB and p38 using wild-type, IKK-depleted, 
      and p38 inhibitor-treated mouse bone marrow-derived macrophages (BMDMs). In 
      silico analysis of transcription factor binding sites was used to predict the 
      potential synergistic transcription factors from the co-expressed genes. Among 
      these genes, NF-kappaB and C/EBPbeta, a p38 downstream transcription factor, were 
      predicted to co-regulate genes in LPS-stimulated BMDMs. Based on the subsequent 
      results of a chromatin immunoprecipitation assay and TNFAIP3 expression in 
      C/EBPbeta-ablated macrophages, we demonstrated that Tnfaip3 is regulated by both 
      NF-kappaB and p38-dependent C/EBPbeta. These results identify a novel regulatory 
      mechanism in TLR4-mediated innate immunity.
FAU - Lai, Ting-Yu
AU  - Lai TY
AD  - Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan.
FAU - Wu, Shang-Duen
AU  - Wu SD
FAU - Tsai, Mong-Hsun
AU  - Tsai MH
FAU - Chuang, Eric Y
AU  - Chuang EY
FAU - Chuang, Li-Ling
AU  - Chuang LL
FAU - Hsu, Li-Chung
AU  - Hsu LC
FAU - Lai, Liang-Chuan
AU  - Lai LC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130902
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factor RelA)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - Cell Line
MH  - Chromatin Immunoprecipitation
MH  - Cysteine Endopeptidases/*genetics
MH  - DNA-Binding Proteins/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Lipopolysaccharides/pharmacology
MH  - *Macrophage Activation/drug effects
MH  - Macrophages/cytology/drug effects/*immunology/metabolism
MH  - Mice
MH  - Promoter Regions, Genetic/genetics
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 4/metabolism
MH  - Transcription Factor RelA/*metabolism
MH  - *Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
MH  - Ubiquitin-Protein Ligases/genetics
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC3759409
COIS- Competing Interests: The co-author Eric Y. Chuang is a PLOS ONE Editorial Board 
      member. However, this does not alter the authors' adherence to all the PLOS ONE 
      policies on sharing data and materials.
EDAT- 2013/09/12 06:00
MHDA- 2014/04/09 06:00
PMCR- 2013/09/02
CRDT- 2013/09/12 06:00
PHST- 2013/02/19 00:00 [received]
PHST- 2013/07/17 00:00 [accepted]
PHST- 2013/09/12 06:00 [entrez]
PHST- 2013/09/12 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
PHST- 2013/09/02 00:00 [pmc-release]
AID - PONE-D-13-07722 [pii]
AID - 10.1371/journal.pone.0073153 [doi]
PST - epublish
SO  - PLoS One. 2013 Sep 2;8(9):e73153. doi: 10.1371/journal.pone.0073153. eCollection 
      2013.