Effect of piceatannol in human monocyte-derived dendritic cells in vitro.
Piceatannol is an anti-inflammatory, immunomodulatory, and antiproliferative stilbene that has been shown to interfere with the cytokine signaling pathway. Dendritic cells (DCs) play a pivotal in the initiation of T-cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. This study investigated the effect of piceatannol on the phenotypic and functional maturation of human monocyte-derived DCs in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days, followed by another 2 days in the presence of piceatannol or LPS. DCs harvested on day 8 were examined using functional assays. The expression levels of CD1a, CD80, CD83, and CD86 as expressed by mean fluorescence intensity (MFI) on DCs differentiated from immature DCs after culture with 1 muM of piceatannol for 2 days were enhanced and decreased endocytic activity. Piceatannol-treated DCs also displayed enhanced T-cell stimulatory capacity in a MLR, as measured by T-cell proliferation. Similar results were obtained with DCs differentiated with LPS from immature DCs. However, piceatannol did not inhibit phenotypic and functional maturation induced by LPS from immature DCs. Piceatannol-treated DCs induced the differentiation of naive T cells towards a helper T-cell type 1 (Th1) response at DCs/T (1:5) cells ratio depending on IL-12 secretion. These results demonstrate that piceatannol may be used on DC-based vaccine for cancer immunotherapy.
Takei
Masao
M
Division of Cellular Allergology, Research Center Borstel, Parkallee 22, D-23845, Borstel, Germany. mtakei@fz-horstel.de
Umeyama
Akemi
A
Arihara
Shigenobu
S
Matsumoto
Hitoshi
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000187:drug effects*; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
D000911:Antibodies, Monoclonal; D003470:Culture Media; D016207:Cytokines; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D013267:Stilbenes; D018664:Interleukin-12; C041525:3,3',4,5'-tetrahydroxystilbene