PMID- 19302817
OWN - NLM
STAT- MEDLINE
DCOM- 20090522
LR  - 20090420
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 84
IP  - 13-14
DP  - 2009 Mar 27
TI  - TNFalpha- and NF-kappaB-dependent induction of the chemokine CCL1 in human 
      macrophages exposed to the atherogenic lipoprotein(a).
PG  - 451-7
LID - 10.1016/j.lfs.2009.01.012 [doi]
AB  - AIMS: CCL1 is a chemokine thought to contribute to cardiovascular diseases and 
      recently reported to be regulated by the pro-atherogenic lipoprotein(a) (Lp(a)) 
      and the ligand-activated aryl hydrocarbon receptor (AhR). The present study was 
      designed to investigate molecular regulatory pathways involved in Lp(a)-mediated 
      induction of CCL1. MAIN METHODS: CCL1 regulation was studied in Lp(a)-exposed 
      human primary macrophages using mainly quantitative reverse 
      transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and 
      electrophoretic mobility shift assay (EMSA). KEY FINDINGS: Using the AhR 
      antagonist alpha-napthtoflavone, the translational inhibitor cycloheximide and 
      anti-tumor necrosis factor alpha (TNFalpha) neutralizing antibodies, we 
      demonstrated that Lp(a)-mediated mRNA induction of CCL1 occurs in an 
      AhR-independent manner and requires de novo protein synthesis of TNFalpha. 
      Involvement of this cytokine was further underlined by the fact that it increased 
      expression and secretion of CCL1 by itself in macrophages. DNA binding activity 
      of NF-kappaB, a well-known molecular effector of TNFalpha, was moreover activated 
      by Lp(a) in a TNFalpha-dependent manner and the use of the NF-kappaB inhibitor 
      Bay 11-7082 blocked Lp(a)-triggered CCL1 induction. In addition, Lp(a) induced 
      binding of NF-kappaB to a NF-kappaB consensus element on CCL1 promoter as 
      assessed by EMSA. Co-exposure to Lp(a) and the AhR ligand benzo(a)pyrene was 
      finally shown to superinduce CCL1 expression in human macrophages, supporting the 
      conclusion that Lp(a) and AhR ligands act on CCL1 through independent ways. 
      SIGNIFICANCE: These data suggest that Lp(a)-triggered induction of CCL1 
      expression is mediated by TNFalpha and subsequent activation of NF-kappaB, 
      without AhR involvement.
FAU - N'Diaye, Monique
AU  - N'Diaye M
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) U620/UPRES 
      SeRAIC, Universite de Rennes-1, IFR140, 35043 Rennes Cedex, France.
FAU - Le Ferrec, Eric
AU  - Le Ferrec E
FAU - Kronenberg, Florian
AU  - Kronenberg F
FAU - Dieplinger, Hans
AU  - Dieplinger H
FAU - Le Vee, Marc
AU  - Le Vee M
FAU - Fardel, Olivier
AU  - Fardel O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090202
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (CCL1 protein, human)
RN  - 0 (Chemokine CCL1)
RN  - 0 (Lipoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Atherosclerosis/etiology/immunology/*metabolism
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Chemokine CCL1/*biosynthesis
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Lipoproteins/blood/*pharmacology
MH  - Macrophages/*drug effects/immunology/metabolism
MH  - NF-kappa B/*metabolism
MH  - Receptors, Aryl Hydrocarbon/antagonists & inhibitors/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 2009/03/24 09:00
MHDA- 2009/05/23 09:00
CRDT- 2009/03/24 09:00
PHST- 2008/08/22 00:00 [received]
PHST- 2008/12/19 00:00 [revised]
PHST- 2009/01/21 00:00 [accepted]
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2009/05/23 09:00 [medline]
AID - S0024-3205(09)00040-X [pii]
AID - 10.1016/j.lfs.2009.01.012 [doi]
PST - ppublish
SO  - Life Sci. 2009 Mar 27;84(13-14):451-7. doi: 10.1016/j.lfs.2009.01.012. Epub 2009 
      Feb 2.