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HMG-CoA Reductase Inhibitors (Statins) Activate Expression of PPARα/PPARγ and ABCA1 in Cultured Gallbladder Epithelial Cells

In gallbladder epithelial cells (GBEC), PPARα and PPARγ ligands modulate inflammation by suppression of TNFα production and prevent excessive accumulation of cholesterol by ABCA1 activation. Recently, HMG-CoA reductase inhibitors (statins) were shown to activate PPARα and PPARγ in various cells but...

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Published in:Digestive diseases and sciences 2010-02, Vol.55 (2), p.292-299
Main Authors: Lee, Jin, Hong, Eun Mi, Koh, Dong Hee, Choi, Min Ho, Jang, Hyun Joo, Kae, Sea Hyub, Choi, Ho Soon
Format: Article
Language:English
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Summary:In gallbladder epithelial cells (GBEC), PPARα and PPARγ ligands modulate inflammation by suppression of TNFα production and prevent excessive accumulation of cholesterol by ABCA1 activation. Recently, HMG-CoA reductase inhibitors (statins) were shown to activate PPARα and PPARγ in various cells but no studies of their effects in GBEC have been conducted. The objective of this study was, therefore, to determine the effects of statins on PPAR and ABCA1 expression and the anti-inflammatory effect of statins in GBEC. Canine GBEC were cultured on Petri dishes. Expression of the proteins PPARα, PPARγ, and ABCA1 was measured by western blotting analysis after treatment with simvastatin, pravastatin, NO-pravastatin, PPARα ligand, or PPARγ ligand in the culture media. Expression of ABCA1 and LXRα mRNAs was estimated by RT-PCR. Expression of TNFα mRNA was measured by RT-PCR after 24 h pre-treatment with the statins, preceding 1 h of lipopolysaccharide (LPS) loading. Simvastatin, pravastatin, and NO-pravastatin increased expression of the proteins PPARα, PPARγ, and ABCA1, and expression of the mRNA of ABCA1 and LXRα in GBEC. Pre-treatment with simvastatin, pravastatin, and NO-pravastatin suppressed the production of TNFα mRNA induced by LPS. In conclusion, statins probably contribute to the preservation of GBEC function by activation of PPARα and PPARγ, which have anti-inflammatory effects by suppression of pro-inflammatory cytokines, and ABCA1 activation mediated by LXRα, which prevents the accumulation of cholesterol in GBEC.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-009-0734-3