Abstract: 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% ± 1.55 vs. 26.3% ± 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.
Keywords: Tribbles; atherosclerosis; macrophages; mouse
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Sung, H.Y.; Francis, S.E.; Arnold, N.D.; Holland, K.; Ernst, V.; Angyal, A.; Kiss-Toth, E. Enhanced Macrophage Tribbles-1 Expression in Murine Experimental Atherosclerosis. Biology 2012, 1, 43-57.
Sung HY, Francis SE, Arnold ND, Holland K, Ernst V, Angyal A, Kiss-Toth E. Enhanced Macrophage Tribbles-1 Expression in Murine Experimental Atherosclerosis. Biology. 2012; 1(1):43-57.
Sung, Hye Youn; Francis, Sheila E.; Arnold, Nadine D.; Holland, Karen; Ernst, Vanessa; Angyal, Adrienn; Kiss-Toth, Endre. 2012. "Enhanced Macrophage Tribbles-1 Expression in Murine Experimental Atherosclerosis." Biology 1, no. 1: 43-57.