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

作者：Xiao, Ji; Chen, Quan; Tang, Dan; Ou, Weiwei; Wang, Jiazheng; Mo, Zhongcheng; Tang, Chaoke; Peng, Liangyu^*; Wang, Deming^*

来源：Acta Biochimica et Biophysica Sinica, 2017, 49(3): 277-283.

DOI：10.1093/abbs/gmw136

• liver X receptor
• cytokine
• mRNA decay
• tristetraprolin
• mitogen-activated protein kinase

Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in posttranscriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1 beta, IL-6 and TNFa mRNA degradation. Moreover, T0901317 destabilized TNFa 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.

• 出版日期2017-3
• 单位南华大学