%0 Journal Article
%T Enhanced Macrophage Tribbles-1 Expression in Murine Experimental Atherosclerosis
%A Hye Youn Sung
%A Sheila E. Francis
%A Nadine D. Arnold
%A Karen Holland
%A Vanessa Ernst
%A Adrienn Angyal
%A Endre Kiss-Toth
%J Biology
%D 2012
%I MDPI AG
%R 10.3390/biology1010043
%X Development of the atherosclerotic plaque involves a complex interplay between a number of cell types and an extensive inter-cellular communication via cell bound as well as soluble mediators. The family of tribbles proteins has recently been identified as novel controllers of pro-inflammatory signal transduction. The objective of this study was to address the expression pattern of all three tribbles proteins in atherosclerotic plaques from a mouse model of atherosclerosis. Each tribbles were expressed in vascular smooth muscle cells, endothelial cells as well as in resident macrophages of mouse atherosclerotic plaques. The role of IL-1 mediated inflammatory events in controlling tribbles expression was also addressed by inducing experimental atherosclerosis in ApoE £¿/£¿IL1R1 £¿/£¿ (double knockout) mice. Immunohistochemical analysis of these mice showed a selective decrease in the percentage of trb-1 expressing macrophages, compared to the ApoE £¿/£¿ cohort (14.7% ¡À 1.55 vs. 26.3% ¡À 1.19). The biological significance of this finding was verified in vitro where overexpression of trb-1 in macrophages led to a significant attenuation (~70%) of IL-6 production as well as a suppressed IL-12 expression induced by a proinflammatory stimulus. In this in vitro setting, expression of truncated trb-1 mutants suggests that the kinase domain of this protein is sufficient to exert this inhibitory action.
%K Tribbles
%K atherosclerosis
%K macrophages
%K mouse
%U http://www.mdpi.com/2079-7737/1/1/43