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.


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.
Ge
Junbo
J
Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, People's Republic of China. gejunbo@zshospital.net
Jia
Qingzhe
Q
Liang
Chun
C
Luo
Yukun
Y
Huang
Dong
D
Sun
Aijun
A
Wang
Keqiang
K
Zou
Yunzeng
Y
Chen
Haozhu
H
D000873:Anthracenes / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000097802:CD83 Antigen
D000873:Anthracenes; D000906:Antibodies; D015703:Antigens, CD; D017127:Glycation End Products, Advanced; D007136:Immunoglobulins; D018664:Interleukin-12; D048031:JNK Mitogen-Activated Protein Kinases; D008562:Membrane Glycoproteins; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D012710:Serum Albumin, Bovine; D000097802:CD83 Antigen; C081628:advanced glycation end products-bovine serum albumin; C432165:pyrazolanthrone