Document Detail


Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells.
MedLine Citation:
PMID:  20572914     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVE: 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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
Authors:
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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of periodontal research     Volume:  45     ISSN:  1600-0765     ISO Abbreviation:  J. Periodont. Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0055107     Medline TA:  J Periodontal Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  720-30     Citation Subset:  D; IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
Affiliation:
Clinical Research Center for Periodontal Diseases, School of Dentistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
5P30NS047463/NS/NINDS NIH HHS; R01 DE017223/DE/NIDCR NIH HHS

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