Lithocholic acid down-regulation of NF-kappaB activity through vitamin D receptor in colonic cancer cells

J Steroid Biochem Mol Biol. 2008 Jul;111(1-2):37-40. doi: 10.1016/j.jsbmb.2008.01.003. Epub 2008 Apr 25.


Lithocholic acid (LCA), a secondary bile acid, is a vitamin D receptor (VDR) ligand. 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the hormonal form of vitamin D, is involved in the anti-inflammatory action through VDR. Therefore, we hypothesize that LCA acts like 1,25(OH)(2)D(3) to drive anti-inflammatory signals. In present study, we used human colonic cancer cells to assess the role of LCA in regulation of the pro-inflammatory NF-kappaB pathway. We found that LCA treatment increased VDR levels, mimicking the effect of 1,25(OH)(2)D(3). LCA pretreatment inhibited the IL-1beta-induced IkappaBalpha degradation and decreased the NF-kappaB p65 phosphorylation. We also measured the production of IL-8, a well-known NF-kappaB target gene, as a read-out of the biological effect of LCA expression on NF-kappaB pathway. LCA significantly decreased IL-8 secretion induced by IL-1beta. These LCA-induced effects were very similar to those of 1,25(OH)(2)D(3.) Thus, LCA recapitulated the effects of 1,25(OH)(2)D(3) on IL-1beta stimulated cells. Mouse embryonic fibroblast (MEF) cells lacking VDR have intrinsically high NF-kappaB activity. LCA pretreatment was not able to prevent TNFalpha-induced IkappaBalpha degradation in MEF VDR (-/-), whereas LCA stabilized IkappaBalpha in MEF VDR (+/-) cells. Collectively, our data indicated that LCA activated the VDR to block inflammatory signals in colon cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Line, Tumor
  • Clone Cells
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Down-Regulation / drug effects*
  • HT29 Cells
  • Humans
  • Lithocholic Acid / metabolism
  • Lithocholic Acid / pharmacology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Receptors, Calcitriol / drug effects*
  • Receptors, Calcitriol / metabolism


  • NF-kappa B
  • Receptors, Calcitriol
  • Lithocholic Acid