PMID- 19152916
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20211020
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 205
IP  - 1
DP  - 2009 Jul
TI  - The up-regulation of monocyte chemoattractant protein-1 (MCP-1) in Ea.hy 926 
      endothelial cells under long-term low folate stress is mediated by the p38 MAPK 
      pathway.
PG  - 48-54
LID - 10.1016/j.atherosclerosis.2008.12.008 [doi]
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1), encoded by the CCL2 gene, 
      plays an important role in the initiation and progression of atherosclerosis. 
      Ea.hy 926 endothelial cells grown under low folate conditions (LO cells) 
      synthesize more MCP-1 mRNA and secrete more MCP-1 protein than folate-replete 
      control cells (HI cells). We investigated the mechanisms underlying the 
      modulation of MCP-1 expression by long-term "folate stress". METHODS AND RESULTS: 
      CCL2 transcription, assessed using promoter-reporter assays, is up-regulated in 
      LO cells relative to HI cells, whereas MCP-1 mRNA stability is unchanged. This 
      quantitative transcriptional bias under chronic low folate conditions is not 
      attributable to differences in active NF-kappaB, but is associated with elevated 
      levels of both total p38 and phospho-p38 that are detectable by Western 
      immunoblotting. Transient, acute methotrexate-mediated folate depletion or 
      exposure to high concentrations of homocysteine (Hcy) had no effect on MCP-1 
      synthesis by Ea.hy 926 cells. The p38 inhibitor SB-203580 abolished the excess 
      MCP-1 production by LO cells. The quantitative transcriptional bias of CCL2 in LO 
      cells was retained following massive induction by TNF-alpha. CONCLUSION: During 
      long-term folate stress, p38 is the primary determinant of CCL2 transcription. 
      Long-term folate insufficiency "primes" Ea.hy 926 endothelial cells to have a 
      quantitatively more vigorous response to cytokine-mediated inflammatory stress.
FAU - Lu, Zhi-Yong
AU  - Lu ZY
AD  - Department of Pharmacology, University of Pennsylvania School of Medicine, 
      Philadelphia, PA 19104, United States.
FAU - Jensen, Liselotte E
AU  - Jensen LE
FAU - Huang, Yuehua
AU  - Huang Y
FAU - Kealey, Carmel
AU  - Kealey C
FAU - Blair, Ian A
AU  - Blair IA
FAU - Whitehead, Alexander S
AU  - Whitehead AS
LA  - eng
GR  - R01 HD039195/HD/NICHD NIH HHS/United States
GR  - AR47663/AR/NIAMS NIH HHS/United States
GR  - R01 AR047663-05/AR/NIAMS NIH HHS/United States
GR  - R01 HD039195-03/HD/NICHD NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - P20 RR020741/RR/NCRR NIH HHS/United States
GR  - ES013508/ES/NIEHS NIH HHS/United States
GR  - P30 ES013508-02/ES/NIEHS NIH HHS/United States
GR  - P20RR020741/RR/NCRR NIH HHS/United States
GR  - R01 AR047663/AR/NIAMS NIH HHS/United States
GR  - P20 RR020741-03/RR/NCRR NIH HHS/United States
GR  - HD039195/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081213
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Folic Acid Antagonists)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Atherosclerosis/*metabolism
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis/*physiology
MH  - Cytokines/metabolism
MH  - Disease Progression
MH  - Enzyme Inhibitors/pharmacology
MH  - Folic Acid/*metabolism
MH  - Folic Acid Antagonists/pharmacology
MH  - Humans
MH  - Inflammation
MH  - Methotrexate/pharmacology
MH  - Models, Biological
MH  - Transcription, Genetic
MH  - *Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC2715998
MID - NIHMS83050
EDAT- 2009/01/21 09:00
MHDA- 2009/08/26 09:00
PMCR- 2010/07/01
CRDT- 2009/01/21 09:00
PHST- 2008/06/03 00:00 [received]
PHST- 2008/12/03 00:00 [revised]
PHST- 2008/12/04 00:00 [accepted]
PHST- 2009/01/21 09:00 [entrez]
PHST- 2009/01/21 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - S0021-9150(08)00850-2 [pii]
AID - 10.1016/j.atherosclerosis.2008.12.008 [doi]
PST - ppublish
SO  - Atherosclerosis. 2009 Jul;205(1):48-54. doi: 
      10.1016/j.atherosclerosis.2008.12.008. Epub 2008 Dec 13.