PMID- 20572914
OWN - NLM
STAT- MEDLINE
DCOM- 20110222
LR  - 20231213
IS  - 1600-0765 (Electronic)
IS  - 0022-3484 (Linking)
VI  - 45
IP  - 6
DP  - 2010 Dec
TI  - Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid 
      production of proinflammatory cytokines by dendritic cells and natural killer 
      cells.
PG  - 720-30
LID - 10.1111/j.1600-0765.2010.01292.x [doi]
AB  - 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-gamma (IFN-gamma) was available. In 
      leukocyte cultures, natural killer (NK) cells rapidly produced IFN-gamma (</= 48 h) 
      when interacting with IL-12-producing DCs activated by anti-PC-opsonized mmLDL. 
      Moreover, IFN-gamma 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-gamma 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.
CI  - (c) 2010 John Wiley & Sons A/S.
FAU - Kikuchi, T
AU  - Kikuchi T
AD  - Clinical Research Center for Periodontal Diseases, School of Dentistry, Medical 
      College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
FAU - El Shikh, M M
AU  - El Shikh MM
FAU - El Sayed, R M
AU  - El Sayed RM
FAU - Purkall, D B
AU  - Purkall DB
FAU - Elaasser, M M
AU  - Elaasser MM
FAU - Sarraf, A
AU  - Sarraf A
FAU - Barbour, S E
AU  - Barbour SE
FAU - Schenkein, H A
AU  - Schenkein HA
FAU - Tew, J G
AU  - Tew JG
LA  - eng
GR  - 5P30NS047463/NS/NINDS NIH HHS/United States
GR  - R01 DE017223/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-12 Subunit p35)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Opsonin Proteins)
RN  - 107-73-3 (Phosphorylcholine)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Aggregatibacter actinomycetemcomitans
MH  - Analysis of Variance
MH  - Antibodies
MH  - Antigens, CD/biosynthesis
MH  - Atherosclerosis/etiology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/*biosynthesis
MH  - Dendritic Cells/immunology/*metabolism
MH  - Humans
MH  - Immunoglobulins/biosynthesis
MH  - Inflammation Mediators/metabolism
MH  - Interferon-gamma/metabolism
MH  - Interleukin-12 Subunit p35/biosynthesis
MH  - Interleukin-12 Subunit p40/biosynthesis
MH  - Killer Cells, Natural/immunology/*metabolism
MH  - Lipoproteins, LDL/*immunology
MH  - Membrane Glycoproteins/biosynthesis
MH  - Opsonin Proteins/*immunology
MH  - Phosphorylcholine/*immunology
MH  - Porphyromonas gingivalis
MH  - Statistics, Nonparametric
MH  - CD83 Antigen
EDAT- 2010/06/25 06:00
MHDA- 2011/02/23 06:00
CRDT- 2010/06/25 06:00
PHST- 2010/06/25 06:00 [entrez]
PHST- 2010/06/25 06:00 [pubmed]
PHST- 2011/02/23 06:00 [medline]
AID - JRE1292 [pii]
AID - 10.1111/j.1600-0765.2010.01292.x [doi]
PST - ppublish
SO  - J Periodontal Res. 2010 Dec;45(6):720-30. doi: 10.1111/j.1600-0765.2010.01292.x.