Interaction among vitamin D(3) analogue KH 1060, TNF-alpha, and vitamin D receptor protein in peripheral blood mononuclear cells of inflammatory bowel disease patients

Int Immunopharmacol. 2006 Jul;6(7):1083-92. doi: 10.1016/j.intimp.2006.01.018. Epub 2006 Feb 23.

Abstract

Background: The active form of vitamin D, 1,25(OH)(2)D(3), exerts important effects on proliferation and differentiation of many cell types, and immunoregulatory activities in particular on T cell-mediated immunity.

Aim: The aim of this study was to investigate whether KH 1060, a vitamin D analogue, could decrease tumor necrosis factor-alpha (TNF-alpha) levels in patients with inflammatory bowel disease (IBD).

Methods: PBMC proliferation was determined by [(3)H]thymidine incorporation. TNF-alpha levels were measured by ELISA kit; VDR, Bcl-2 and Bax protein levels with Western blot analysis.

Results: KH 1060 inhibited PBMC proliferation and decreased TNF-alpha levels in IBD patients and this effect was synergistic with anti-TNF-alpha. VDR protein levels were significantly increased by PBMC treatment with KH 1060 or anti-TNF-alpha or their combination in ulcerative colitis (UC) patients, and decreased in Crohn's disease (CD) patients, treating the cells with KH 1060. In UC patients an increase in Bcl-2 and Bax levels was observed incubating, PBMC with KH 1060 or anti-TNF-alpha or their combination. In CD patients a slight decrease in Bcl-2 levels was registered when anti-TNF alone or in association with KH 1060 was used. Bax protein levels were slightly increased in the presence of KH 1060 alone or in combination with anti-TNF.

Conclusion: This study shows that KH 1060 acts as an immunomodulator on PBMC, acting as TNF-alpha inhibitor. This finding provides strong evidence that vitamin D status could be an important regulator of immunity IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Inflammatory Bowel Diseases / blood*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Infliximab
  • Leukocytes, Mononuclear / drug effects*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Calcitriol / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antibodies, Monoclonal
  • BAX protein, human
  • Immunosuppressive Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Calcitriol
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • KH 1060
  • Infliximab
  • Calcitriol