The effect of Malononitrilamides (FK778) on phenotypic properties of human peripheral dendritic cells.
BACKGROUND
FK778, a malononitrilamide analogue of lefunomide, is currently a promising immunosuppressive drug. Because the cellular and molecular mechanisms underlying the effects of FK778 are not entirely clarified. We studied its effects on human peripheral dendritic cells.


METHODS
Peripheral blood mononuclear cells (PBMC) from 12 healthy volunteers were isolated by density separation over Ficoll solution. After resuspension in adaptive immunotherapy medium (AIM)-V medium, they were cultured without exogenous growth factors. The study group was treated with FK 778 (50 microg/mL) or Rapamycin (10 ng/mL). The phenotype of dendritic cell was ascertained by indirect immunoflurescence for analysis by flow cytometry.


RESULTS
Compared with the Rapamycin-treated controls, the expressions of CD80, CD83, CD86, HLA-DA, CD54, CD62, CCR5, and CCR7 in the FK778-treated myeloid dendritic cells and the expression of CD80, CD83, CD86, HLA-DA, and CD54 in the FK778-treated plasmacytoid dendritic cells were significantly down-regulated.


CONCLUSIONS
FK778 inhibited the differentiation and maturation of dendritic cells.
Hou
J
J
Department of Intensive Care Unit, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Wei
J-M
JM
Yu
Z-Y
ZY
Xu
Y
Y
Li
J
J
Tang
D N
DN
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D009570:Nitriles / Q000494:pharmacology*; D010641:Phenotype; D012016:Reference Values; D020123:Sirolimus / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000480:Alkynes; D015703:Antigens, CD; D007555:Isoxazoles; D009570:Nitriles; C115284:2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide; D000077339:Leflunomide; D020123:Sirolimus