PMID- 19265715
OWN - NLM
STAT- MEDLINE
DCOM- 20090609
LR  - 20211020
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 237
IP  - 1
DP  - 2009 May 15
TI  - Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 
      is caveolin-1-dependent.
PG  - 1-7
LID - 10.1016/j.taap.2009.02.016 [doi]
AB  - Atherosclerosis, the primary cause of heart disease and stroke is initiated in 
      the vascular endothelium, and risk factors for its development include 
      environmental exposure to persistent organic pollutants. Caveolae are membrane 
      microdomains involved in regulation of many signaling pathways, and in particular 
      in endothelial cells. We tested the hypothesis that intact caveolae are required 
      for coplanar PCB77-induced up-regulation of monocyte chemoattractant protein-1 
      (MCP-1), an endothelium-derived chemokine that attracts monocytes into 
      sub-endothelial space in early stages of the atherosclerosis development. 
      Atherosclerosis-prone LDL-R(-/-) mice (control) or caveolin-1(-/-)/LDL-R(-/-) 
      mice were treated with PCB77. PCB77 induced aortic mRNA expression and plasma 
      protein levels of MCP-1 in control, but not caveolin-1(-/-)/LDL-R(-/-) mice. To 
      study the mechanism of this effect, primary endothelial cells were used. PCB77 
      increased MCP-1 levels in endothelial cells in a time- and 
      concentration-dependent manner. This effect was abolished by caveolin-1 silencing 
      using siRNA. Also, MCP-1 up-regulation by PCB77 was prevented by inhibiting p38 
      and c-Jun N-terminal kinase (JNK), but not ERK1/2, suggesting regulatory 
      functions via p38 and JNK MAPK pathways. Finally, pre-treatment of endothelial 
      cells with the aryl hydrocarbon receptor (AhR) inhibitor alpha-naphthoflavone 
      (alpha-NF) partially blocked MCP-1 up-regulation. Thus, our data demonstrate that 
      coplanar PCB77 can induce MCP-1 expression by endothelial cells and that this 
      effect is mediated by AhR, as well as p 38 and JNK MAPK pathways. Intact caveolae 
      are required for these processes both in vivo and in vitro. This further supports 
      a key role for caveolae in vascular inflammation induced by persistent organic 
      pollutants.
FAU - Majkova, Zuzana
AU  - Majkova Z
AD  - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536-0200, 
      USA.
FAU - Smart, Eric
AU  - Smart E
FAU - Toborek, Michal
AU  - Toborek M
FAU - Hennig, Bernhard
AU  - Hennig B
LA  - eng
GR  - R01 CA133257/CA/NCI NIH HHS/United States
GR  - R01 MH063022/MH/NIMH NIH HHS/United States
GR  - P42ES07380/ES/NIEHS NIH HHS/United States
GR  - R01 NS039254-05/NS/NINDS NIH HHS/United States
GR  - R01 MH063022-05/MH/NIMH NIH HHS/United States
GR  - P42 ES007380-139005/ES/NIEHS NIH HHS/United States
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - R01 DA027569/DA/NIDA NIH HHS/United States
GR  - R01 NS039254/NS/NINDS NIH HHS/United States
GR  - P42 ES007380-130009/ES/NIEHS NIH HHS/United States
GR  - R01 MH098891/MH/NIMH NIH HHS/United States
GR  - R01 MH072567/MH/NIMH NIH HHS/United States
GR  - P42 ES007380-12/ES/NIEHS NIH HHS/United States
GR  - R01 MH072567-04/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090302
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Caveolin 1)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Environmental Pollutants)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, LDL)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Atherosclerosis/chemically induced/genetics/*metabolism
MH  - Caveolae/drug effects/metabolism
MH  - Caveolin 1/*drug effects/genetics/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/drug effects/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/cytology/drug effects/*metabolism
MH  - Environmental Pollutants/*toxicity
MH  - Gene Expression Regulation/drug effects
MH  - Gene Silencing/physiology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Polychlorinated Biphenyls/*toxicity
MH  - RNA, Messenger/analysis
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Aryl Hydrocarbon/drug effects/metabolism
MH  - Receptors, LDL/deficiency/genetics
MH  - Second Messenger Systems
MH  - Signal Transduction/drug effects/physiology
MH  - Statistics, Nonparametric
MH  - Swine
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC2680936
MID - NIHMS100416
EDAT- 2009/03/07 09:00
MHDA- 2009/06/10 09:00
PMCR- 2010/05/15
CRDT- 2009/03/07 09:00
PHST- 2009/01/08 00:00 [received]
PHST- 2009/02/11 00:00 [revised]
PHST- 2009/02/13 00:00 [accepted]
PHST- 2009/03/07 09:00 [entrez]
PHST- 2009/03/07 09:00 [pubmed]
PHST- 2009/06/10 09:00 [medline]
PHST- 2010/05/15 00:00 [pmc-release]
AID - S0041-008X(09)00084-2 [pii]
AID - 10.1016/j.taap.2009.02.016 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2009 May 15;237(1):1-7. doi: 10.1016/j.taap.2009.02.016. 
      Epub 2009 Mar 2.