Enhanced macrophage tribbles-1 expression in murine experimental atherosclerosis.
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.
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. dowellyoun@yahoo.co.kr.
Hye Youn
HY
Sung
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. s.francis@sheffield.ac.uk.
Sheila E
SE
Francis
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. n.d.arnold@sheffield.ac.uk.
Nadine D
ND
Arnold
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. k.holland@sheffield.ac.uk.
Karen
K
Holland
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. vanessa.ernst@fh-krems.eu.
Vanessa
V
Ernst
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. a.angyal@sheffield.ac.uk.
Adrienn
A
Angyal
Department of Cardiovascular Science, University of Sheffield, Sheffield, S10 2RX, UK. e.kiss-toth@sheffield.ac.uk.
Endre
E
Kiss-Toth