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
2024-03-28
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References

  1. Akira S. 2003; Toll-like receptor signaling. J Biol Chem 278:38105–38108 [CrossRef]
    [Google Scholar]
  2. Akira S., Takeda K. 2004; Toll-like receptor signalling. Nat Rev Immunol 4:499–511 [CrossRef]
    [Google Scholar]
  3. Aliprantis A. O., Yang R.-B., Mark M. R., Suggett S., Devaux B., Radolf J. D., Klimpel G. R., Godowski P., Zychlinsky A. 1999; Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 285:736–739 [CrossRef]
    [Google Scholar]
  4. Banchereau J., Steinman R. M. 1998; Dendritic cells and the control of immunity. Nature 392:245–252 [CrossRef]
    [Google Scholar]
  5. Brightbill H. D., Plevy S. E., Modlin R. L., Smale S. T. 2000; A prominent role for Sp1 during lipopolysaccharide-mediated induction of the IL-10 promoter in macrophages. J Immunol 164:1940–1951 [CrossRef]
    [Google Scholar]
  6. Cutler C. W., Jotwani R., Palucka K. A., Davoust J., Bell D., Banchereau J. 1999; Evidence and a novel hypothesis for the role of dendritic cells and Porphyromonas gingivalis in adult periodontitis. J Periodontal Res 34:406–412 [CrossRef]
    [Google Scholar]
  7. De Smedt T., Pajak B., Muraille E., Lespagnard L., Heinen E., De Baetselier P., Urbain J., Leo O., Moser M. 1996; Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J Exp Med 184:1413–1424 [CrossRef]
    [Google Scholar]
  8. Dillon S., Agrawal A., Van Dyke T., Landreth G., McCauley L., Koh A., Maliszewski C., Akira S., Pulendran B. 2004; A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 172:4733–4743 [CrossRef]
    [Google Scholar]
  9. Drakes M., Blanchard T., Czinn S. 2004; Bacterial probiotic modulation of dendritic cells. Infect Immun 72:3299–3309 [CrossRef]
    [Google Scholar]
  10. Gemmell E., Carter C. L., Hart D. N., Drysdale K. E., Seymour G. J. 2002; Antigen-presenting cells in human periodontal disease tissues. Oral Microbiol Immunol 17:388–393 [CrossRef]
    [Google Scholar]
  11. Hashimoto M., Asai Y., Ogawa T. 2004; Separation and structural analysis of lipoprotein in a lipopolysaccharide preparation from Porphyromonas gingivalis . Int Immunol 16:1431–1437 [CrossRef]
    [Google Scholar]
  12. Hertz C. J., Kiertscher S. M., Godowski P. J., Bouis D. A., Norgard M. V., Roth M. D., Modlin R. L. 2001; Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. J Immunol 166:2444–2450 [CrossRef]
    [Google Scholar]
  13. Holt S. C., Kesavalu L., Walker S., Genco C. A. 1999; Virulence factors of Porphyromonas gingivalis . Periodontol 2000; 20:168–238 [CrossRef]
    [Google Scholar]
  14. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S. 1999; Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752
    [Google Scholar]
  15. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. 1993; Development of TH1 CD4+ T cells through IL-12 produced by Listeria -induced macrophages. Science 260:547–549 [CrossRef]
    [Google Scholar]
  16. Imler J. L., Hoffmann J. A. 2003; Toll signaling: the TIReless quest for specificity. Nat Immunol 4:105–106
    [Google Scholar]
  17. Imoto M., Yoshimura N., Kusumoto S., Shiba T. 1984; Total synthesis of lipid A, active principle of bacterial endotoxin. Proc Jpn Acad Ser B 60:285–288 [CrossRef]
    [Google Scholar]
  18. Jotwani R., Cutler C. W. 2003; Multiple dendritic cell (DC) subpopulations in human gingiva and association of mature DCs with CD4+ T-cells in situ. J Dent Res 82:736–741 [CrossRef]
    [Google Scholar]
  19. Jotwani R., Palucka A. K., Al-Quotub M., Nouri-Shirazi M., Kim J., Bell D., Banchereau J., Cutler C. W. 2001; Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. J Immunol 167:4693–4700 [CrossRef]
    [Google Scholar]
  20. Kawai T., Akira S. 2005; Pathogen recognition with Toll-like receptors. Curr Opin Immunol 17:338–344 [CrossRef]
    [Google Scholar]
  21. Kiura K., Kataoka H., Nakata T., Into T., Yasuda M., Akira S., Inoue N., Shibata K. 2006; The synthetic analogue of mycoplasmal lipoprotein FSL-1 induces dendritic cell maturation through Toll-like receptor 2. FEMS Immunol Med Microbiol 46:78–84 [CrossRef]
    [Google Scholar]
  22. Lin Y.-L., Liang Y.-C., Lee S.-S., Chiang B.-L. 2005; Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF- κ B and p38 mitogen-activated protein kinase pathways. J Leukoc Biol 78:533–543 [CrossRef]
    [Google Scholar]
  23. Lutz M. B., Kukutsch N., Ogilvie A. L., Rossner S., Koch F., Romani N., Schuler G. 1999; An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods 223:77–92 [CrossRef]
    [Google Scholar]
  24. Makimura Y., Asai Y., Taiji Y., Sugiyama A., Tamai R., Ogawa T. 2006; Correlation between chemical structure and biological activities of Porphyromonas gingivalis synthetic lipopeptide derivatives. Clin Exp Immunol 146:159–168 [CrossRef]
    [Google Scholar]
  25. Mellman I., Steinman R. M. 2001; Dendritic cells: specialized and regulated antigen processing machines. Cell 106:255–258 [CrossRef]
    [Google Scholar]
  26. Nishiguchi M., Matsumoto M., Takao T., Hoshino M., Shimonishi Y., Tsuji S., Begum N. A., Takeuchi O., Akira S. other authors 2001; Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2: role of N-terminal hydrophobic portion in its multiple functions. J Immunol 166:2610–2616 [CrossRef]
    [Google Scholar]
  27. Offenbacher S. 1996; Periodontal diseases: pathogenesis. Ann Periodontol 1:821–878 [CrossRef]
    [Google Scholar]
  28. Palucka K., Banchereau J. 2002; How dendritic cells and microbes interact to elicit or subvert protective immune responses. Curr Opin Immunol 14:420–431 [CrossRef]
    [Google Scholar]
  29. Rescigno M., Granucci F., Ricciardi-Castagnoli P. 2000; Molecular events of bacterial-induced maturation of dendritic cells. J Clin Immunol 20:161–166 [CrossRef]
    [Google Scholar]
  30. Rincon M., Anguita J., Nakamura T., Fikrig E., Flavell R. A. 1997; Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells. J Exp Med 185:461–469 [CrossRef]
    [Google Scholar]
  31. Seguier S., Godeau G., Leborgne M., Pivert G., Brousse N. 2000; Quantitative morphological analysis of Langerhans cells inhealthy and diseased human gingiva. Arch Oral Biol 45:1073–1081 [CrossRef]
    [Google Scholar]
  32. Singleton T. E., Massari P., Wetzler L. M. 2005; Neisserial porin-induced dendritic cell activation is MyD88 and TLR2 dependent. J Immunol 174:3545–3550 [CrossRef]
    [Google Scholar]
  33. Slots J., Bragd L., Wikstrom M., Dahlen G. 1986; The occurrence of Actinobacillus actinomycetemcomitans , Bacteroides gingivalis and Bacteroides intermedius in destructive periodontal disease in adults. J Clin Periodontol 13:570–577 [CrossRef]
    [Google Scholar]
  34. Sparwasser T., Koch E. S., Vabulas R. M., Heeg K., Lipford G. B., Ellwart J. W., Wagner H. 1998; Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol 28:2045–2054 [CrossRef]
    [Google Scholar]
  35. Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., Shamel L., Sovath S. other authors 2004; Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 101:3516–3521 [CrossRef]
    [Google Scholar]
  36. Takeuchi O., Kawai T., Muhlradt P. F., Morr M., Radolf J. D., Zychlinsky A., Takeda K., Akira S. 2001; Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13:933–940 [CrossRef]
    [Google Scholar]
  37. Takeuchi O., Sato S., Horiuchi T., Hoshino K., Takeda K., Dong Z., Modlin R. L., Akira S. 2002; Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14 [CrossRef]
    [Google Scholar]
  38. Wallet M. A., Sen P., Tisch R. 2005; Immunoregulation of dendritic cells. Clin Med Res 3:166–175 [CrossRef]
    [Google Scholar]
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