Visit our Expo - Redox and Inflammation signaling 2012

Session IX. Novel compounds targeting inflammatory signaling pathways Poster IX, 7
DiC14-amidine cationic lipid induces the production of IL-12 by murine bone-marrow
derived dendritic cells: importance of TLR-4 and JNK
Tetsuya Tanaka1), Michel Vandenbranden2), Jean-Marie Ruysschaert2) and Alain
Jacquet1).
1)Service de Génétique Appliquée, Institut de Biologie et de Médecine Moléculaires,
Université Libre de Bruxelles, B-6041 Gosselies, Belgium and 2)Laboratoire "Structure
et Fonction des Membranes Biologiques," Université Libre de Bruxelles, Campus
Plaine, B-1050 Brussels, Belgium E-mail : tetsuyat2003@hotmail.com
DiC14-amidine cationic lipid has been shown to act as a Th1-adjuvant. A recombinant form
of the major mite allergen Der p 1 (ProDer p 1) complexed with diC 14-amidine prevented the
development of typical Th2-biased allergic response in mice. The present study investigates
the effect of diC14-amidine on murine bone-marrow-derived dendritic cells (BMDC) and
particularly at the level of the pro-Th1 cytokine IL-12 production.
BMDC exhibited IL-12 but not IL-10 secretion when stimulated with diC14-amidine,
complexed or not with ProDer p 1. The recombinant allergen did not induce cytokine
production. Using BMDCs from TLR4- and TLR2-deficient mice, we clearly demonstrated
that diC14-amidine stimulation of dendritic cells involved TLR4 but not TLR2. Although all
three MAP kinases, ERK1/2, p38 and JNK were activated, diC14-amidine induced IL-12
release exclusively via the JNK signaling pathway. Finally, IL-12 release induced by the
cationic lipid correlated with degradation of IkB, a critical step in NF-kB activation. In
conclusion, the activation of dendritic cells by the complex ProDer p 1-amidine leading to IL-
12 production could explain the development of Th1-biased immune response by this vaccine.
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