title: [Effects and mechanism of hyperglycemia on development and maturation and immune function of human monocyte derived dendritic cells].
abstract: OBJECTIVE
  Dendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs).
  
  
  METHODS
  Immature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques.
  
  
  RESULTS
  Compared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC.
  
  
  CONCLUSIONS
  High glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai 200032, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yao
authors.forename: Jun-bo
authors.initials: JB
authors.lastname: Ge
authors.forename: Ai-jun
authors.initials: AJ
authors.lastname: Sun
authors.forename: Xiao-wu
authors.initials: XW
authors.lastname: Hong
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Shi
authors.forename: Rong-chong
authors.initials: RC
authors.lastname: Huang
authors.forename: Qing-zhe
authors.initials: QZ
authors.lastname: Jia
authors.forename: Ke-qiang
authors.initials: KQ
authors.lastname: Wang
authors.forename: Cui-ping
authors.initials: CP
authors.lastname: Zhong
authors.forename: Xue-tao
authors.initials: XT
authors.lastname: Cao
authors.forename: Yun-zeng
authors.initials: YZ
authors.lastname: Zou
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005947:Glucose / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D009000:Monocytes / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D003470:Culture Media; D016207:Cytokines; D017382:Reactive Oxygen Species; D005947:Glucose