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Título

Inhibition of lipopolysaccharide-induced gene expression by liver X receptor ligands in macrophages involves interference with early growth response factor 1

AutorGuillem-Llobat, Paloma; Íñiguez, Miguel Ángel
Palabras claveMacrophages
mPGES-1
COX-2
LXR
RXR
Egr-1
Fecha de publicación2015
CitaciónProstaglandins Leukotrienes and Essential Fatty Acids 96: 37- 49 (2015)
Resumen© 2015 Elsevier Ltd. 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 NFκB, 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.
URIhttp://hdl.handle.net/10261/139539
DOI10.1016/j.plefa.2015.02.002
Identificadoresdoi: 10.1016/j.plefa.2015.02.002
issn: 1532-2823
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