DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4.

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.

Disciplines :

Genetics & genetic processes

Author, co-author :

Tanaka, Tetsuya

Legat, Amandine

Adam, Emmanuelle

Steuve, Jonathan

GATOT, Jean-Stéphane ; Centre Hospitalier Universitaire de Liège - CHU > Génétique

Vandenbranden, Michel

Ulianov, Liliana

Lonez, Caroline

Ruysschaert, Jean-Marie

Muraille, Eric

More authors (3 more)

Language :

English

Title :

DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4.

Publication date :

2008

Journal title :

European Journal of Immunology

ISSN :

0014-2980

eISSN :

1521-4141

Publisher :

John Wiley & Sons, United Kingdom

Volume :

Issue :

Pages :

1351-7

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 26 November 2014

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