Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells
| Autor: | T, Kikuchi, M M, El Shikh, R M, El Sayed, D B, Purkall, M M, Elaasser, A, Sarraf, S E, Barbour, H A, Schenkein, J G, Tew |
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| Rok vydání: | 2010 |
| Předmět: |
Analysis of Variance
Membrane Glycoproteins Interleukin-12 Subunit p40 Phosphorylcholine Immunoglobulins Dendritic Cells Opsonin Proteins Atherosclerosis Aggregatibacter actinomycetemcomitans Antibodies Coculture Techniques Interleukin-12 Subunit p35 Statistics Nonparametric Killer Cells Natural Lipoproteins LDL Interferon-gamma Antigens CD Cytokines Humans Inflammation Mediators Porphyromonas gingivalis Cells Cultured |
| Zdroj: | Journal of periodontal research. 45(6) |
| ISSN: | 1600-0765 |
| Popis: | Epidemiological and animal studies suggest that periodontal infections increase atherosclerosis risk. Periodontitis patients have elevated levels of anti-phosphorylcholine (anti-PC) reactive not only with numerous periodontal organisms but also with minimally modified low-density lipoprotein (mmLDL). Dendritic cells (DCs) reside in arterial walls and accumulate in atherosclerotic lesions. The ability of anti-PC to bind mmLDL prompted the hypothesis that opsonized mmLDL would stimulate DCs and enhance the production of proinflammatory cytokines that promote atherogenic plaque development.Monocyte-derived DCs (mDCs) were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, then stimulated with mmLDL or with anti-PC-opsonized mmLDL. The anti-PC effect was determined using flow cytometry, cofocal microscopy and cytokine assays. The production of CD83, IL-12p35 mRNA, IL-12p40 mRNA, IL-12p70 and IL-10 by DCs was monitored.Dendritic cells stimulated with mmLDL expressed little CD83 and produced little IL-12p70. However, anti-PC-opsonized mmLDL enhanced DC maturation, as indicated by upregulated CD83 and rapid (≤ 48 h) production of IL-12p70 if a source of interferon-γ (IFN-γ) was available. In leukocyte cultures, natural killer (NK) cells rapidly produced IFN-γ (≤ 48 h) when interacting with IL-12-producing DCs activated by anti-PC-opsonized mmLDL. Moreover, IFN-γ promoted DC IL-12 responses that were further augmented when mmLDL was opsonized with anti-PC.Minimally modified LDL-stimulated DCs and NK cells were mutually stimulatory, with DC IL-12p70 needed by NK cells and with NK cell IFN-γ needed by DCs. Moreover, production of these proinflammatory cytokines was markedly enhanced when LDL was opsonized by anti-PC. In short, the data suggest that the elevated anti-PC levels in periodontitis patients could promote a mechanism that facilitates atherosclerosis. |
| Databáze: | OpenAIRE |
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