title: 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.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. maria.stio@unifi.it
authors.forename: Maria
authors.initials: M
authors.lastname: Stio
authors.forename: Maria
authors.initials: M
authors.lastname: Martinesi
authors.forename: Sara
authors.initials: S
authors.lastname: Bruni
authors.forename: Cristina
authors.initials: C
authors.lastname: Treves
authors.forename: Giuseppe
authors.initials: G
authors.lastname: d'Albasio
authors.forename: Siro
authors.initials: S
authors.lastname: Bagnoli
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Bonanomi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D000069285:Infliximab; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C494826:BAX protein, human; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C074279:KH 1060; D000069285:Infliximab; D002117:Calcitriol