1. Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro.
- Author
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Jingti Deng, Christian H. James, Lisa Patel, Alberto Smith, Kevin G. Burnand, Hassan Rahmoune, Jonathan R. Lamb, and Bill Davis
- Subjects
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PROTEIN kinases , *TUMOR necrosis factors , *ATHEROSCLEROTIC plaque , *CAROTID artery diseases , *INTERLEUKIN-10 , *GENE expression , *GENETIC regulation , *MESSENGER RNA , *GENETICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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