In gallbladder epithelial cells (GBEC), PPARalpha and PPARgamma ligands modulate 
inflammation by suppression of TNFalpha production and prevent excessive 
accumulation of cholesterol by ABCA1 activation. Recently, HMG-CoA reductase 
inhibitors (statins) were shown to activate PPARalpha and PPARgamma 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 PPARalpha, 
PPARgamma, and ABCA1 was measured by western blotting analysis after treatment 
with simvastatin, pravastatin, NO-pravastatin, PPARalpha ligand, or PPARgamma 
ligand in the culture media. Expression of ABCA1 and LXRalpha mRNAs was 
estimated by RT-PCR. Expression of TNFalpha 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 PPARalpha, PPARgamma, and ABCA1, and expression of the mRNA of 
ABCA1 and LXRalpha in GBEC. Pre-treatment with simvastatin, pravastatin, and 
NO-pravastatin suppressed the production of TNFalpha mRNA induced by LPS. In 
conclusion, statins probably contribute to the preservation of GBEC function by 
activation of PPARalpha and PPARgamma, which have anti-inflammatory effects by 
suppression of pro-inflammatory cytokines, and ABCA1 activation mediated by 
LXRalpha, which prevents the accumulation of cholesterol in GBEC.