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Publication : A recombinant lipoprotein containing an unsaturated fatty acid activates NF-kappaB through the TLR2 signaling pathway and induces a differential gene profile from a synthetic lipopeptide.

First Author  Leng CH Year  2010
Journal  Mol Immunol Volume  47
Issue  11-12 Pages  2015-21
PubMed ID  20478617 Mgi Jnum  J:160689
Mgi Id  MGI:4454946 Doi  10.1016/j.molimm.2010.04.012
Citation  Leng CH, et al. (2010) A recombinant lipoprotein containing an unsaturated fatty acid activates NF-kappaB through the TLR2 signaling pathway and induces a differential gene profile from a synthetic lipopeptide. Mol Immunol 47(11-12):2015-21
abstractText  The lipid moiety of a novel recombinant lipoprotein, which contains a dengue virus envelope protein domain 3, rlipo-D1E3, has been shown to activate antigen-presenting cells (APCs) as an intrinsic adjuvant. Because the lipid moiety of rlipo-D1E3 contains an unsaturated fatty acid, it is unclear if the receptor usage by bacterially derived lipoproteins is the same as that of the synthetic lipopeptide palmitoyl-3-Cys-Ser-(Lys)(4) (Pam3). In the present study, we show that the rlipo-D1E3 lipoprotein can induce the activation of spleen cells and bone marrow-derived dendritic cells (BM-DCs) in wild-type and TLR4-deficient mice, but not in TLR2(-/-) mice. After analyzing the co-receptor usage of TLR2 using TLR1(-/-) or TLR6(-/-) mice, the TLR2 signaling triggered by rlipo-D1E3 and Pam3 could use either TLR1 or TLR6 as a co-receptor. Analysis of the MAPK signaling pathway revealed that rlipo-D1E3 could initiate the phosphorylation of p38, ERK1/2 and JNK1/2 earlier than the synthetic lipopeptide. In addition, the expression levels of IL-23, IL-27 and MIP-1 alpha in BM-DCs stimulated by rlipo-D1E3 were higher than the expression levels in BM-DCs stimulated by Pam3. Taken together, these results demonstrate that different TLR2 ligands can promote various immune responses by inducing different levels of biological cytokines and chemokines.
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