PMID- 15537384
OWN - NLM
STAT- MEDLINE
DCOM- 20051020
LR  - 20220318
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 387
IP  - Pt 2
DP  - 2005 Apr 15
TI  - Critical role for Ets, AP-1 and GATA-like transcription factors in regulating 
      mouse Toll-like receptor 4 (Tlr4) gene expression.
PG  - 355-65
AB  - TLR4 (Toll-like receptor 4) is essential for sensing the endotoxin of 
      Gram-negative bacteria. Mutations or deletion of the TLR4 gene in humans or mice 
      have been associated with altered predisposition to or outcome of Gram-negative 
      sepsis. In the present work, we studied the expression and regulation of the Tlr4 
      gene of mouse. In vivo, TLR4 levels were higher in macrophages compared with B, T 
      or natural killer cells. High basal TLR4 promoter activity was observed in RAW 
      264.7, J774 and P388D1 macrophages transfected with a TLR4 promoter reporter 
      vector. Analysis of truncated and mutated promoter constructs identified several 
      positive [two Ets (E twenty-six) and one AP-1 (activator protein-1) sites] and 
      negative (a GATA-like site and an octamer site) regulatory elements within 350 bp 
      upstream of the transcriptional start site. The myeloid and B-cell-specific 
      transcription factor PU.1 bound to the proximal Ets site. In contrast, none among 
      PU.1, Ets-1, Ets-2 and Elk-1, but possibly one member of the ESE 
      (epithelium-specific Ets) subfamily of Ets transcription factors, bound to the 
      distal Ets site, which was indispensable for Tlr4 gene transcription. Endotoxin 
      did not affect macrophage TLR4 promoter activity, but it decreased TLR4 
      steady-state mRNA levels by increasing the turnover of TLR4 transcripts. TLR4 
      expression was modestly altered by other pro- and anti-inflammatory stimuli, 
      except for PMA plus ionomycin which strongly increased promoter activity and TLR4 
      mRNA levels. The mouse and human TLR4 genes were highly conserved. Yet, notable 
      differences exist with respect to the elements implicated in gene regulation, 
      which may account for species differences in terms of tissue expression and 
      modulation by microbial and inflammatory stimuli.
FAU - Roger, Thierry
AU  - Roger T
AD  - Infectious Diseases Service, Department of Internal Medicine, Centre Hospitalier 
      Universitaire Vaudois, BH19-111, rue du Bugnon 46, CH-1011 Lausanne, Switzerland. 
      Thierry.Roger@chuv.ch
FAU - Miconnet, Isabelle
AU  - Miconnet I
FAU - Schiesser, Anne-Laure
AU  - Schiesser AL
FAU - Kai, Hirofumi
AU  - Kai H
FAU - Miyake, Kensuke
AU  - Miyake K
FAU - Calandra, Thierry
AU  - Calandra T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DNA-Binding Proteins/physiology
MH  - Gene Expression Regulation/*physiology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mutation
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Receptors, Immunologic/*biosynthesis/genetics
MH  - Toll-Like Receptor 4
MH  - Transcription Factors/*physiology
PMC - PMC1134963
EDAT- 2004/11/13 09:00
MHDA- 2005/10/21 09:00
PMCR- 2005/10/15
CRDT- 2004/11/13 09:00
PHST- 2004/11/13 09:00 [pubmed]
PHST- 2005/10/21 09:00 [medline]
PHST- 2004/11/13 09:00 [entrez]
PHST- 2005/10/15 00:00 [pmc-release]
AID - BJ20041243 [pii]
AID - bj3870355 [pii]
AID - 10.1042/BJ20041243 [doi]
PST - ppublish
SO  - Biochem J. 2005 Apr 15;387(Pt 2):355-65. doi: 10.1042/BJ20041243.