title: 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.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ou
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Jiazheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, University of South China, Hengyang 421001, China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Mo
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, China.
authors.forename: Chaoke
authors.initials: C
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D000071518:Liver X Receptors / Q000819:agonists / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D020413:3' Untranslated Regions; D048049:Extracellular Signal-Regulated MAP Kinases; D006845:Hydrocarbons, Fluorinated; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D012333:RNA, Messenger; D013449:Sulfonamides; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: cytokine; liver X receptor; mRNA decay; mitogen-activated protein kinase; tristetraprolin