PMID- 20652710
OWN - NLM
STAT- MEDLINE
DCOM- 20110811
LR  - 20240109
IS  - 1436-6215 (Electronic)
IS  - 1436-6207 (Linking)
VI  - 50
IP  - 3
DP  - 2011 Apr
TI  - Immunoregulatory effects of the flavonol quercetin in vitro and in vivo.
PG  - 163-72
LID - 10.1007/s00394-010-0125-8 [doi]
AB  - PURPOSE: Atherosclerosis is known to be an inflammatory disease. Dendritic cells 
      (DCs) are essential for the regulation of the immune system. Up to 10% of the 
      cells in atherosclerotic plaques are DCs. The cardiovascular protective effects 
      of flavonoids (tea, wine) may be mediated by anti-inflammatory mechanisms that 
      affect DC regulation. We aimed to characterize the impact of the flavonol 
      quercetin on DC activity and differentiation in vitro and in vivo. METHODS: For 
      the in vitro experiments, we used murine DCs and endothelial cells to study 
      adhesion properties. For all other experiments (DC phagocytosis capacity, DC 
      maturation, DC differentiation (BDCA-1/-2) and NF-kB-activation), human 
      monocyte-derived DCs were used. The cells were incubated with quercetin 
      (10 mumol/L) +/- oxLDL (10 mug/mL) between 24 and 48 h. For in vivo experiments, 
      eight healthy male volunteers took 500 mg of quercetin twice daily over 4 weeks, 
      five healthy male volunteers served as control. Before and after intake, blood 
      samples were collected. Peripheral blood leukocytes were isolated (analyses of DC 
      differentiation), and plasma was immediately frozen. RESULTS: Quercetin reduced 
      DC adhesion (-42%; p < 0.05) and expression of CD11a (-21%; p < 0.05). 
      OxLDL-induced DC differentiation was partially inhibited by quercetin 
      (BDCA-1-29%; BDCA-2-33%; p < 0.05). These effects were achieved by compensation 
      of oxLDL-induced up-regulation of NF-kB by quercetin. The 4-week treatment with 
      quercetin resulted in relevant plasma levels (2.47 mumol/L) and reduced 
      BDCA-2 + DCs in the peripheral blood by 42% (p < 0.05) as well as systemic levels 
      of the NO-synthase inhibitor asymmetric dimethylarginine (-31%, p < 0.05). 
      CONCLUSION: In vitro, quercetin reduced DC adhesion and oxLDL-induced DC 
      differentiation. In vivo, quercetin reduced circulating plasmacytoid DCs and 
      systemic ADMA-levels. The immunoregulatory effects of quercetin may contribute to 
      the anti-atherosclerotic potential of flavonols.
FAU - Nickel, Thomas
AU  - Nickel T
AD  - Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians and 
      University of Munich, 81377, Munich, Germany. tsnickel@web.de
FAU - Hanssen, Henner
AU  - Hanssen H
FAU - Sisic, Zeljka
AU  - Sisic Z
FAU - Pfeiler, Susanne
AU  - Pfeiler S
FAU - Summo, Claudia
AU  - Summo C
FAU - Schmauss, Daniel
AU  - Schmauss D
FAU - Hoster, Eva
AU  - Hoster E
FAU - Weis, Michael
AU  - Weis M
LA  - eng
PT  - Journal Article
DEP - 20100723
PL  - Germany
TA  - Eur J Nutr
JT  - European journal of nutrition
JID - 100888704
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (NF-kappa B)
RN  - 0 (oxidized low density lipoprotein)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Apoptosis
MH  - Arginine/analogs & derivatives/blood
MH  - Cell Adhesion
MH  - Cell Differentiation
MH  - Cell Line
MH  - Dendritic Cells/immunology/*metabolism
MH  - Endocytosis
MH  - Endothelial Cells/metabolism
MH  - Humans
MH  - Leukocytes/metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/cytology/immunology
MH  - NF-kappa B/drug effects
MH  - Quercetin/*blood/*pharmacology
MH  - Up-Regulation
EDAT- 2010/07/24 06:00
MHDA- 2011/08/13 06:00
CRDT- 2010/07/24 06:00
PHST- 2009/12/09 00:00 [received]
PHST- 2010/07/08 00:00 [accepted]
PHST- 2010/07/24 06:00 [entrez]
PHST- 2010/07/24 06:00 [pubmed]
PHST- 2011/08/13 06:00 [medline]
AID - 10.1007/s00394-010-0125-8 [doi]
PST - ppublish
SO  - Eur J Nutr. 2011 Apr;50(3):163-72. doi: 10.1007/s00394-010-0125-8. Epub 2010 Jul 
      23.