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The Interleukin-1 receptor antagonist is a direct target gene of PPARalpha in liver.

Abstract：

BACKGROUND/AIMS:The Peroxisome Proliferator-Activated Receptor (PPAR) alpha belongs to the superfamily of Nuclear Receptors and plays an important role in numerous cellular processes, including lipid metabolism. It is known that PPARalpha also has an anti-inflammatory effect, which is mainly achieved by down-regulating pro-inflammatory genes. The objective of this study was to further characterize the role of PPARalpha in inflammatory gene regulation in liver. RESULTS:According to Affymetrix micro-array analysis, the expression of various inflammatory genes in liver was decreased by treatment of mice with the synthetic PPARalpha agonist Wy14643 in a PPARalpha-dependent manner. In contrast, expression of Interleukin-1 receptor antagonist (IL-1ra), which was acutely stimulated by LPS treatment, was induced by PPARalpha. Up-regulation of IL-1ra by LPS was lower in PPARalpha -/- mice compared to Wt mice. Transactivation and chromatin immunoprecipitation studies identified IL-1ra as a direct positive target gene of PPARalpha with a functional PPRE present in the promoter. Up-regulation of IL-1ra by PPARalpha was conserved in human HepG2 hepatoma cells and the human monocyte/macrophage THP-1 cell line. CONCLUSIONS:In addition to down-regulating expression of pro-inflammatory genes, PPARalpha suppresses the inflammatory response by direct up-regulation of genes with anti-inflammatory properties.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Stienstra R,Mandard S,Tan NS,Wahli W,Trautwein C,Richardson TA,Lichtenauer-Kaligis E,Kersten S,Müller M

doi

10.1016/j.jhep.2006.11.019

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

869-77

issue

5

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(06)00672-6

journal_volume

46

pub_type

杂志文章

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