Health & Environmental Research Online (HERO)


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567204 
Journal Article 
New insights into mechanism for the effect of probucol in anti-atherosclerosis: Possible role of inhibitor on immune maturation of dendritic cells 
Jin, X; Sun, A; Wang, K; Zou, Y; Ge, J 
2008 
1 
5 
260-262 
Atherosclerosis is a chronic inflammatory disease whose lesions are filled with various immune cells and cytokines. In particular, dendritic cells (DCs) are potent antigen-presenting and immune-modulating cells that have been implicated for the important role of inducing and modulating immune responses in the development of atherosclerosis recently. Notably, before activating T lymphocytes, immature DCs need to undergo "immune maturation" in which various pro- and anti-inflammatory cytokines have participated. Probucol, an agent characterized by lipid-lowering and anti-oxidant property, retards atherosclerosis effectively, while its underlying mechanism remains poorly understood. In the present article, we propose that probucol exerts its therapeutic anti-atherosclerosis effect mainly through inhibiting immune maturation of DCs. Our hypothesis is based on the background that probucol up-regulates heme oxygenase-1(HO-1), its target molecular, and leads to resultant reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines in atherogenesis. Through comparative analysis of immunophenotypic expression, endocytosis function and cytokines secretions of DCs between control group and experimental group intervened by probucol in vivo and in vitro, we aim to evaluate the influence of probucol on immune maturation of DCs. Moreover, our hypothesis aims to not only offer an alternative, novel approach for better understanding the mechanism of probucol, but also provide further evidence to support the significant role of DCs in atherosclerosis and may implicate DCs as another therapeutic target in management of atherosclerosis and other inflammation induced vascular disease. 
Atherosclerosis; Dendritic cells; Probucol; Heme oxygenase-1