PMID- 25736222
OWN - NLM
STAT- MEDLINE
DCOM- 20151228
LR  - 20161125
IS  - 1532-2823 (Electronic)
IS  - 0952-3278 (Linking)
VI  - 96
DP  - 2015 May
TI  - Inhibition of lipopolysaccharide-induced gene expression by liver X receptor 
      ligands in macrophages involves interference with early growth response factor 1.
PG  - 37-49
LID - S0952-3278(15)00044-7 [pii]
LID - 10.1016/j.plefa.2015.02.002 [doi]
AB  - Liver X receptors (LXRs) are nuclear receptors that act as ligand-dependent 
      transcription factors forming permissive heterodimers with retinoid X receptors 
      (RXRs). In this study we aimed to assess the effect of LXR/RXR activation on the 
      transcriptional induction of pro-inflammatory genes including cyclooxygenase-2 
      (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in activated 
      macrophages. Our study shows that LXR ligands such as oxysterols, GW3965 or 
      TO901317, as well as RXR ligands like 9cis retinoic acid or SR11237, decreased 
      LPS-induced expression of COX-2 and mPGES-1. Consequently, LPS-dependent PGE2 
      production was substantially reduced in macrophages treated with LXR/RXR ligands. 
      The inhibitory effects of LXR/RXR activation on LPS-induced expression of COX-2 
      and mPGES-1 in macrophages, occurred by a mechanism involving interference with 
      transcriptional activation of these genes. LXR/RXR activation interfered with the 
      activity of transcription factors essential in the up-regulation of the 
      expression of pro-inflammatory genes in these cells, such as NFkappaB, but also 
      Egr-1, which had not been previously associated with LXR-mediated gene 
      repression. As this transcription factor is involved in the regulation of a 
      variety of genes involved in inflammatory processes, LXR and RXR-mediated 
      interference with Egr-1 signaling could represent an important event mediating 
      the anti-inflammatory effects of these receptors in macrophages.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Guillem-Llobat, Paloma
AU  - Guillem-Llobat P
AD  - Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Departamento de Biologia 
      Molecular, Instituto de Investigacion Sanitaria Princesa, Universidad Autonoma de 
      Madrid, Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid, Spain.
FAU - Iniguez, Miguel A
AU  - Iniguez MA
AD  - Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Departamento de Biologia 
      Molecular, Instituto de Investigacion Sanitaria Princesa, Universidad Autonoma de 
      Madrid, Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid, Spain. Electronic address: 
      mainiguez@cbm.csic.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150219
PL  - Scotland
TA  - Prostaglandins Leukot Essent Fatty Acids
JT  - Prostaglandins, leukotrienes, and essential fatty acids
JID - 8802730
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Early Growth Response Protein 1/*metabolism
MH  - Gene Expression/*drug effects
MH  - Humans
MH  - Ligands
MH  - Lipopolysaccharides/*metabolism
MH  - Liver X Receptors
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Monocytes/metabolism
MH  - Orphan Nuclear Receptors/antagonists & inhibitors/metabolism/*pharmacology
OTO - NOTNLM
OT  - COX-2
OT  - Egr-1
OT  - LXR
OT  - Macrophages
OT  - RXR
OT  - mPGES-1
EDAT- 2015/03/05 06:00
MHDA- 2015/12/29 06:00
CRDT- 2015/03/05 06:00
PHST- 2014/11/11 00:00 [received]
PHST- 2015/02/09 00:00 [revised]
PHST- 2015/02/10 00:00 [accepted]
PHST- 2015/03/05 06:00 [entrez]
PHST- 2015/03/05 06:00 [pubmed]
PHST- 2015/12/29 06:00 [medline]
AID - S0952-3278(15)00044-7 [pii]
AID - 10.1016/j.plefa.2015.02.002 [doi]
PST - ppublish
SO  - Prostaglandins Leukot Essent Fatty Acids. 2015 May;96:37-49. doi: 
      10.1016/j.plefa.2015.02.002. Epub 2015 Feb 19.