Received for publication September 11, 2008.
Revised November 4, 2008.
Accepted for publication November 5, 2008.

Vitamin D₃ Modulates the Expression of Bile Acid Regulatory Genes and Represses Inflammation in Bile Duct-Ligated Mice

Abstract

Vitamin D receptor (VDR), a nuclear receptor that regulates calcium homeostasis, has been found to function as a receptor for secondary bile acids. Since 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 1-hydroxyvitamin D₃ [1(OH)D₃] after bile duct ligation (BDL) and examined mRNA expression and cytokine levels. 1(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. 1(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 1(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.

Key words: bile acids, cholestasis, inflammation, nuclear receptors, vitamin D, vitamin D recetpor