High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 4474-4480, 2012.
Article
in En
| WPRIM
| ID: wpr-331350
Responsible library:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive.</p><p><b>METHODS</b>In this study, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined.</p><p><b>RESULTS</b>Lp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment (1 - 10 ng/ml) upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARγ phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL.</p><p><b>CONCLUSION</b>These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.</p>
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
/
Signal Transduction
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Cells, Cultured
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Reverse Transcriptase Polymerase Chain Reaction
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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PPAR gamma
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Genetics
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Lipoproteins, HDL
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Macrophages
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Metabolism
Limits:
Humans
Language:
En
Journal:
Chinese Medical Journal
Year:
2012
Type:
Article