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.
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February 2009
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Research Article|
January 08 2009
Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro
Jingti Deng;
Jingti Deng
*GlaxoSmithKline Clinical Unit, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 2GG, U.K.
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Christian H. James;
Christian H. James
†Translational and Regenerative Medicine, GlaxoSmithKline, King of Prussia, PA 19406, U.S.A.
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Lisa Patel;
Lisa Patel
‡Department of Atherosclerosis, Medicines Research Centre, GlaxoSmithKline, Stevenage SG1 2NY, U.K.
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Alberto Smith;
Alberto Smith
§Academic Department of Surgery, Cardiovascular Division, King's College London, St Thomas' Hospital, London SE1 7EH, U.K.
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Kevin G. Burnand;
Kevin G. Burnand
§Academic Department of Surgery, Cardiovascular Division, King's College London, St Thomas' Hospital, London SE1 7EH, U.K.
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Hassan Rahmoune;
Hassan Rahmoune
*GlaxoSmithKline Clinical Unit, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 2GG, U.K.
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Jonathan R. Lamb;
Jonathan R. Lamb
∥Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin EH25 9RG, U.K.
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Bill Davis
Bill Davis
*
*GlaxoSmithKline Clinical Unit, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 2GG, U.K.
Correspondence: Dr Bill Davis (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 21 2008
Revision Received:
July 14 2008
Accepted:
July 21 2008
Accepted Manuscript online:
July 21 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (3): 241–248.
Article history
Received:
February 21 2008
Revision Received:
July 14 2008
Accepted:
July 21 2008
Accepted Manuscript online:
July 21 2008
Citation
Jingti Deng, Christian H. James, Lisa Patel, Alberto Smith, Kevin G. Burnand, Hassan Rahmoune, Jonathan R. Lamb, Bill Davis; Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro. Clin Sci (Lond) 1 February 2009; 116 (3): 241–248. doi: https://doi.org/10.1042/CS20080058
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