RT Journal Article
SR Electronic
T1 Vitamin D<sub>3</sub> Modulates the Expression of Bile Acid Regulatory Genes and Represses Inflammation in Bile Duct-Ligated Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 564
OP 570
DO 10.1124/jpet.108.145987
VO 328
IS 2
A1 Michitaka Ogura
A1 Shigeru Nishida
A1 Michiyasu Ishizawa
A1 Kenichi Sakurai
A1 Makoto Shimizu
A1 Sadanori Matsuo
A1 Sadao Amano
A1 Shigeyuki Uno
A1 Makoto Makishima
YR 2009
UL http://jpet.aspetjournals.org/content/328/2/564.abstract
AB Vitamin D receptor (VDR), a nuclear receptor that regulates calcium homeostasis, has been found to function as a receptor for secondary bile acids. Because the in vivo role of VDR in bile acid metabolism remains unknown, we investigated the effect of VDR activation in a mouse model of cholestasis. We treated mice with 1α-hydroxyvitamin D3 [1α(OH)D3] after bile duct ligation (BDL) and examined mRNA expression and cytokine levels. 1α(OH)D3 treatment altered the expression of genes involved in bile acid synthesis and transport in the liver, kidney, and intestine but did not decrease bile acid levels in the plasma and liver of BDL mice. 1α(OH)D3 treatment suppressed mRNA expression of proinflammatory cytokines in the liver and strongly decreased the plasma levels of proinflammatory cytokines in BDL mice. These findings indicate that 1α(OH)D3 regulates a network of bile acid metabolic genes and represses proinflammatory cytokine expression in BDL mice. VDR ligands have the potential to prevent the cholestasis-induced inflammatory response. The American Society for Pharmacology and Experimental Therapeutics