Keywords :
Adaptor Proteins, Vesicular Transport/genetics; Adjuvants, Immunologic/administration & dosage/pharmacology; Amidines/administration & dosage/pharmacology; Animals; Cell Line; Cytokines/metabolism; Dendritic Cells/drug effects/metabolism; Female; Humans; Interleukin-12 Subunit p40/metabolism; Lymphocyte Antigen 96/genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mitogen-Activated Protein Kinases/metabolism; Myeloid Cells/cytology; Myeloid Differentiation Factor 88/genetics; NF-kappa B/metabolism; Phosphorylation/drug effects; Toll-Like Receptor 4/agonists/genetics; Toll-Like Receptors/genetics; Transfection; Tumor Necrosis Factor-alpha/metabolism
Abstract :
[en] DiC14-amidine cationic liposomes were recently shown to promote Th1 responses when mixed with allergen. To further define the mode of action of diC14-amidine as potential vaccine adjuvant, we characterized its effects on mouse and human myeloid dendritic cells (DC). First, we observed that, as compared with two other cationic liposomes, only diC14-amidine liposomes induced the production of IL-12p40 and TNF-alpha by mouse bone marrow-derived DC. DiC14-amidine liposomes also activated human DC, as shown by synthesis of IL-12p40 and TNF-alpha, accumulation of IL-6, IFN-beta and CXCL10 mRNA, and up-regulation of membrane expression of CD80 and CD86. DC stimulation by diC14-amidine liposomes was associated with activation of NF-kappaB, ERK1/2, JNK and p38 MAP kinases. Finally, we demonstrated in mouse and human cells that diC14-amidine liposomes use Toll-like receptor 4 to elicit both MyD88-dependent and Toll/IL-1R-containing adaptor inducing interferon IFN-beta (TRIF)-dependent responses.
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