1887

Abstract

A PG1828 gene-encoded triacylated lipoprotein was previously isolated from a lipopolysaccharide preparation as a Toll-like receptor (TLR) 2 agonist and its lipopeptide derivatives were synthesized based on the chemical structure. In the present study, granulocyte–macrophage colony stimulating factor-differentiated bone marrow-derived dendritic cells (BMDDCs) were stimulated separately with the synthetic lipopeptide -palmitoyl--[2-pentadecanoyloxy, 3-palmitoyloxy-(2)-propyl]--Cys-Asn-Ser-Gln-Ala-Lys (PGTP2-RL) and its glyceryl stereoisomer (PGTP2-SL). Only PGTP2-RL activated BMDDCs from wild-type mice to secrete tumour necrosis factor-, interleukin (IL)-6, IL-10 and IL-12p40, whilst PGTP2-RL-induced cytokine production was eliminated in TLR2 knockout () BMDDCs. BMDDCs from wild-type mice but not TLR2 mice responded to PGTP2-RL as well as PamCSK by increasing the expression of maturation markers, including CD80 (B7-1), CD86 (B7-2), CD40, CD275 (B7RP-1/inducible T-cell co-stimulatory ligand) and major histocompatibility complex class II. Taken together, these results indicate that the fatty acid residue at the glycerol position in the lipopeptide plays a pivotal role in TLR2-mediated dendritic cell activation.

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2007-04-01
2020-07-15
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