Advanced glycosylation end products might promote atherosclerosis through inducing the immune maturation of dendritic cells

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 [IFN], IFN-gamma, 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.