Toll-like receptor 2-mediated dendritic cell activation by a Porphyromonas gingivalis synthetic lipopeptide.
A PG1828 gene-encoded triacylated lipoprotein was previously isolated from a Porphyromonas gingivalis 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 P. gingivalis synthetic lipopeptide N-palmitoyl-S-[2-pentadecanoyloxy, 3-palmitoyloxy-(2R)-propyl]-l-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-alpha, 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 Pam(3)CSK(4) 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 P. gingivalis lipopeptide plays a pivotal role in TLR2-mediated dendritic cell activation.
Asai
Yasuyuki
Y
Department of Oral Microbiology, Asahi University School of Dentistry, Gifu 501-0296, Japan.
Makimura
Yutaka
Y
Department of Oral Microbiology, Asahi University School of Dentistry, Gifu 501-0296, Japan.
Ogawa
Tomohiko
T
Department of Oral Microbiology, Asahi University School of Dentistry, Gifu 501-0296, Japan.
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D039521:CD11c Antigen; D016207:Cytokines; D008074:Lipoproteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2