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Enhanced Macrophage Tribbles-1 Expression in Murine Experimental Atherosclerosis

Authors :
Adrienn Angyal
Endre Kiss-Toth
Vanessa Ernst
Karen Holland
Nadine D. Arnold
Sheila E. Francis
Hye Youn Sung
Source :
Biology, Vol 1, Iss 1, Pp 43-57 (2012)
Publication Year :
2012
Publisher :
MDPI AG, 2012.

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.

Details

Language :
English
ISSN :
20797737
Volume :
1
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.3644b51c24875b6e6464e688134e3
Document Type :
article
Full Text :
https://doi.org/10.3390/biology1010043