Activation of liver X receptors promotes inflammatory cytokine mRNA degradation by upregulation of tristetraprolin.

Abstract:

:Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFα mRNA degradation. Moreover, T0901317 destabilized TNFα mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay. Interestingly, T0901317 repressed LPS-induced phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) in THP-1 macrophages. The evidence presented here confirms that LXR activation with T0901317 inhibits the phosphorylation of ERK1/2 and p38 MAPK, likely resulting in the increased expression of TTP and the decay of LPS-induce inflammatory cytokine mRNAs.

authors

Xiao J,Chen Q,Tang D,Ou W,Wang J,Mo Z,Tang C,Peng L,Wang D

doi

10.1093/abbs/gmw136

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

277-283

issue

3

eissn

1672-9145

issn

1745-7270

pii

gmw136

journal_volume

49

pub_type

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