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

Jingti Deng , Christian H James , Lisa Patel , Alberto Smith , Kevin G Burnand , Hassan Rahmoune , Jonathan Lamb , Bill Davis (1)

1 Clinical Unit, Cambridge

Mammalian orthologs 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 this study, a screen for mRNA species specifically regulated in vulnerable regions of human atherosclerotic plaque demonstrated upregulation 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 upregulated by treatment with oxidised low density lipoprotein (LDL), and that expression of recombinant Trb2 specifically reduced macrophage levels of IL-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 that may contribute to plaque instability.

Mots clés: Medicine

Jingti Deng, Christian H James, Lisa Patel, Alberto Smith, Kevin G Burnand, et al.. Human tribbles homolog 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro. Clinical Science, 2009, 116 (3), pp.241-248. ⟨10.1042/CS20080058⟩. ⟨hal-00479428⟩