PMID- 19864645
OWN - NLM
STAT- MEDLINE
DCOM- 20100209
LR  - 20231213
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 27
DP  - 2009 Dec 24
TI  - Epigenetic regulation of dendritic cell differentiation and function by oxidized 
      phospholipids.
PG  - 5481-9
LID - 10.1182/blood-2008-11-191429 [doi]
AB  - Dendritic cells (DCs) are the key cell type in the regulation of an adaptive 
      immune response. Under inflammatory conditions monocytes can give rise to 
      immunostimulatory DCs, depending on microenvironmental stimuli. Here we show that 
      oxidized phospholipids (Ox-Pls), which are generated during inflammatory 
      reactions, dysregulate the differentiation of DCs. DCs generated in the presence 
      of Ox-Pls up-regulated the typical DC marker DC-SIGN but did not express CD1a, 
      CD1b, and CD1c. These DCs generated in the presence of Ox-Pls had a substantially 
      diminished T cell-stimulating capacity after stimulation with Toll-like receptor 
      ligands. Toll-like receptor ligand-induced production of interleukin-12 also was 
      strongly diminished, whereas induction of CD83 was not altered. In addition, we 
      found that Ox-Pls strongly inhibit inflammatory stimuli-induced phosphorylation 
      of histone H3, a key step of interleukin-12 production, yet leaving activation of 
      nuclear factor-kappaB unaltered. Taken together, Ox-Pls present during 
      differentiation yielded DCs with a reduced capacity to become immunostimulatory 
      mature DCs. Furthermore, the presence of Ox-Pls blocked histone modifications 
      required for full activation of DCs. Therefore, inflammation-derived Ox-Pls 
      control DC functions in part by epigenetic mechanisms.
FAU - Bluml, Stephan
AU  - Bluml S
AD  - Institute of Immunology, Medical University of Vienna, Vienna, Austria. 
      stephan.blueml@meduniwien.ac.at
FAU - Zupkovitz, Gordin
AU  - Zupkovitz G
FAU - Kirchberger, Stefanie
AU  - Kirchberger S
FAU - Seyerl, Maria
AU  - Seyerl M
FAU - Bochkov, Valery N
AU  - Bochkov VN
FAU - Stuhlmeier, Karl
AU  - Stuhlmeier K
FAU - Majdic, Otto
AU  - Majdic O
FAU - Zlabinger, Gerhard J
AU  - Zlabinger GJ
FAU - Seiser, Christian
AU  - Seiser C
FAU - Stockl, Johannes
AU  - Stockl J
LA  - eng
GR  - P 20266/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091028
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Histones)
RN  - 0 (Immunoglobulins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Antigens, CD/genetics
MH  - Blotting, Western
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Epigenesis, Genetic
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects
MH  - Histones/metabolism
MH  - Humans
MH  - Immunoglobulins/genetics
MH  - Interleukin-12/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Membrane Glycoproteins/genetics
MH  - Monocytes/cytology/*drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphatidylcholines/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes/cytology/drug effects/metabolism
MH  - CD83 Antigen
EDAT- 2009/10/30 06:00
MHDA- 2010/02/10 06:00
CRDT- 2009/10/30 06:00
PHST- 2009/10/30 06:00 [entrez]
PHST- 2009/10/30 06:00 [pubmed]
PHST- 2010/02/10 06:00 [medline]
AID - S0006-4971(20)38768-1 [pii]
AID - 10.1182/blood-2008-11-191429 [doi]
PST - ppublish
SO  - Blood. 2009 Dec 24;114(27):5481-9. doi: 10.1182/blood-2008-11-191429. Epub 2009 
      Oct 28.