on August 11, 2005
Published online before print August 11, 2005, doi: 10.1161/01.ATV.0000181744.58265.63
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Submitted on December 21, 2004
Accepted on June 6, 2005
Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells
Junbo Ge *;
From Shanghai Institute of Cardiovascular Disease (J.G., Q.J., Y.L., D.H., A.S., K.W., Y.Z., H.C.), Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; and the Department of Cardiology (C.L.), Changzheng Hospital, the Second Military Medical University, Shanghai, People’s Republic of China.
* To whom correspondence should be addressed. E-mail: gejunbo{at}zshospital.net.
Objective-- Both advanced glycosylation end products (AGEs) and dendritic cells (DCs) have been shown to play a causative role in atherosclerosis. However, whether they function interactively in the process remains uncertain. We therefore studied the effects of AGE-bovine serum albumin (AGE-BSA) on the maturation of DCs and the expressions of scavenger receptor-A (SR-A) and receptor for AGEs (RAGE) on DCs.
Methods and Results-- AGE-BSA induced DCs maturation accompanied with increased expressions of CD1a, CD40, CD80, CD83, CD86, and MHC class II. The capacity of DCs to stimulate T-cell proliferation and secretion of cytokines (interferon [INF], INF-
, interleukin [IL]-10 and IL-12) was also enhanced by AGE-BSA. AGE-BSA significantly upregulated SR-A and RAGE expression on DCs and the upregulation was abolished by inhibition of mitogen-activated protein (MAP) kinase Jnk, but not by that of Erk and p38 MAP kinase. AGE-BSA-induced expression of CD83 and secretion of IL-12 were partly inhibited by either an anti-RAGE neutralizing antibody or a Jnk inhibitor.
Conclusions-- AGE-BSA induces maturation of DCs and augmented their capacity to stimulate T-cell proliferation and cytokine secretions possibly through upregulation of RAGE and SR-A, which at least in part through Jnk. These findings might explain in part the interactive roles of AGEs and DCs in the processes of atherosclerosis.
Key words: advanced glycosylation end products • atherosclerosis • dendritic cells • immunity • receptor for advanced glycosylation end products
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