[Hyperinsulinemia induced immune maturation of human monocyte derived dendritic cells: bridging between diabetes and atherosclerosis].
OBJECTIVE
Dendritic cells an hyperinsulinemia are both implicated in the pathogenesis of atherosclerosis. The aim of this study is to explore the effect of high concentration of insulin on the maturation of monocyte-derived dendritic cells (MoDCs) and related signal transduction pathways.


METHODS
Human monocytes were purified (over 98%) using Anti-CD14 micro-beads and cultured for 5 days with DC Cellgro medium containing rhGM-CSF (100 microg/L) and rhIL-4 (20 microg/L). Immature DC were then incubated with insulin of various concentrations (0, 1, 10, 100 nmol/L) for 24 hours in the presence or absence of LY294002 (PI3K inhibitor) or PD98059 (MAPK inhibitor). Immunophenotypic expression of CD86 and CD83 were detected using flow cytometry. Endocytosis function of the MoDCs was evaluated using FITC-Dextran and MoDCs secretion IL-12, IFN-gamma and TNF-alpha were measured by ELISA.


RESULTS
Insulin induced significantly higher CD83 and CD86 expressions on MoDCs in a dose-dependent manner. The endocytosis function of MoDCs were significantly inhibited and cytokine secretions of IL-12, IFN-gamma and TNF-alpha significantly increased by 10 nmol/L and 100 nmol/L insulin. These effects could be blocked by the LY294002 and PD98059.


CONCLUSIONS
Hyperinsulinemia contributed to atherosclerosis via stimulating immune maturation of MoDCs via both PI3K and MAPK pathways.
Lu
Hao
H
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai 200032, China.
Qian
Ju-ying
JY
Yao
Kang
K
Sun
Ai-jun
AJ
Huang
Rong-chong
RC
Hao
Ying
Y
Shi
Hong-yu
HY
Wang
Ke-qiang
KQ
Zou
Yun-zeng
YZ
Ge
Jun-bo
JB
D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects; D015398:Signal Transduction
D016207:Cytokines; D007328:Insulin