Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro

被引:22
作者
Deng, Jingti [1 ]
James, Christian H. [2 ]
Patel, Lisa [3 ]
Smith, Alberto [4 ]
Burnand, Kevin G. [4 ]
Rahmoune, Hassan [1 ]
Lamb, Jonathan R. [5 ]
Davis, Bill [1 ]
机构
[1] Addenbrookes Hosp, Addenbrookes Ctr Clin Invest, GlaxoSmithKline Clin Unit, Cambridge CB2 2GG, England
[2] GlaxoSmithKline, Translat & Regenerat Med, King Of Prussia, PA 19406 USA
[3] GlaxoSmithKline, Med Res Ctr, Dept Atherosclerosis, Stevenage SG1 2NY, Herts, England
[4] Kings Coll London, St Thomas Hosp, Div Cardiovasc, Acad Dept Surg, London SE1 7EH, England
[5] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9RG, Midlothian, Scotland
关键词
atherosclerosis; interleukin-10 (IL-10); macrophage; tribbles homologue 2 (Trb2); unstable plaque; FOAM CELL-FORMATION; INTERLEUKIN-10; CORONARY; TRB3; ATHEROSCLEROSIS; INFLAMMATION; INHIBITION; ACTIVATION; MECHANISMS; PROMOTER;
D O I
10.1042/CS20080058
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Mammalian orthologues of the Drosophila tribbles protein (Trb1, Trb2 and Trb3) are a recently described family of signalling molecules that regulate gene expression by modulation of protein kinase signalling pathways. In the present study, a screen for mRNA species specifically regulated in vulnerable regions of human atherosclerotic plaque demonstrated the up-regulation of both Trb1 and Trb2, the latter by more than 8-fold. In vitro experiments in primary human monocyte-derived macrophages showed that Trb2 expression was up-regulated by treatment with oxidized LDL (low-density lipoprotein), and that expression of recombinant Trb2 specifically reduced macrophage levels of IL-10 (interleukin-10) mRNA. Our results thus identify Trb2 as a highly regulated gene in vulnerable atherosclerotic lesions, and demonstrate inhibition of macrophage IL-10 biosynthesis as a potential pro-inflammatory consequence of high Trb2 expression, which may contribute to plaque instability.
引用
收藏
页码:241 / 248
页数:8
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