Ciglitazone inhibits oxidized-low density lipoprotein induced immune maturation of dendritic cells.
BACKGROUND
The peroxisome proliferator-activated receptor (PPAR) activation has generally been shown to have anti-inflammatory effects and dendritic cells (DCs) are the most efficient antigen presenting cells that play an active role in the development of atherosclerosis. The effects of PPARgamma on DCs maturation and immune function remain unknown now and we, therefore, studied the influence of PPARgamma agonist ciglitazone on the maturation and immune function of DCs.


METHODS
Human monocytes were purified and immature DCs derived; ciglitazone (25 micromol/L) was added to the medium for 24 hours; ox-LDL (50 microg/ml) was then added to the medium for another 24 hours. The immunophenotypic expressions (CD1a, CD40, CD86, and HLA-DR) were analyzed by FACS and endocytosis function by FITC-dextran and the cytokines secretions of culture supernatants (IL-12,IL-10,TNFalpha, and IL-2) were measured with ELISA.


RESULTS
Ciglitazone reduced ox-LDL induced immunophenotypic expressions of DCs (CD40, CD1a, and HLA-DR). Ox-LDL inhibited the endocytosis of DCs, which was prevented by ciglitazone; ciglitazone attenuated ox-LDL induced cytokine secretions of DCs (IL-12, 116 +/- 29 versus 34 +/- 3 pg/ml*; IL-10, 49 +/- 1 versus 28 +/- 9 pg/ml*; TNFalpha, 46 +/- 16 versus 24 +/- 8 pg/ml*, *P < 0.05 compared with ox-LDL, respectively).


CONCLUSIONS
Our study suggested that one of the anti-inflammatory mechanisms of PPAR-gamma agonist ciglitazone was mediated by inhibiting the ox-LDL induced maturation and immune function of DCs.
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Yukun
Y
Luo
Chun
C
Liang
Congfeng
C
Xu
Qingzhe
Q
Jia
Dong
D
Huang
Lianglong
L
Chen
Keqiang
K
Wang
Zonggui
Z
Wu
Junbo
J
Ge
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D003911:Dextrans; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D006684:HLA-DR Antigens / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D016130:Immunophenotyping / Q000379:methods; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000276:immunology / Q000494:pharmacology; D045162:Thiazolidinediones / Q000276:immunology / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D015703:Antigens, CD; D018949:Antigens, CD1; D051940:B7-2 Antigen; C419393:CD1a antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D003911:Dextrans; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C015219:fluorescein isothiocyanate dextran; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D018664:Interleukin-12; D016650:Fluorescein-5-isothiocyanate; C039671:ciglitazone