PMID- 19225884
OWN - NLM
STAT- MEDLINE
DCOM- 20100218
LR  - 20211020
IS  - 1573-2568 (Electronic)
IS  - 0163-2116 (Linking)
VI  - 55
IP  - 2
DP  - 2010 Feb
TI  - HMG-CoA reductase inhibitors (statins) activate expression of PPARalpha/PPARgamma 
      and ABCA1 in cultured gallbladder epithelial cells.
PG  - 292-9
LID - 10.1007/s10620-009-0734-3 [doi]
AB  - 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.
FAU - Lee, Jin
AU  - Lee J
AD  - Division of Gastroenterology, Department of Internal Medicine, College of 
      Medicine, Hangang Sacred Heart Hospital, Hallym University, Youngdungpo-Gu, 
      Seoul, Korea. jinlee@medimail.co.kr
FAU - Hong, Eun Mi
AU  - Hong EM
FAU - Koh, Dong Hee
AU  - Koh DH
FAU - Choi, Min Ho
AU  - Choi MH
FAU - Jang, Hyun Joo
AU  - Jang HJ
FAU - Kae, Sea Hyub
AU  - Kae SH
FAU - Choi, Ho Soon
AU  - Choi HS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090219
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - ATP Binding Cassette Transporter 1
MH  - ATP-Binding Cassette Transporters/biosynthesis/drug effects/*genetics
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Dogs
MH  - Epithelial Cells/cytology/drug effects/metabolism
MH  - Gallbladder/*cytology/drug effects/metabolism
MH  - Gene Expression/*drug effects
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - PPAR alpha/biosynthesis/*genetics
MH  - PPAR gamma/biosynthesis/*genetics
MH  - RNA, Messenger/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2009/02/20 09:00
MHDA- 2010/02/19 06:00
CRDT- 2009/02/20 09:00
PHST- 2008/10/15 00:00 [received]
PHST- 2009/01/16 00:00 [accepted]
PHST- 2009/02/20 09:00 [entrez]
PHST- 2009/02/20 09:00 [pubmed]
PHST- 2010/02/19 06:00 [medline]
AID - 10.1007/s10620-009-0734-3 [doi]
PST - ppublish
SO  - Dig Dis Sci. 2010 Feb;55(2):292-9. doi: 10.1007/s10620-009-0734-3. Epub 2009 Feb 
      19.