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.
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.
Stio
Maria
M
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. maria.stio@unifi.it
Martinesi
Maria
M
Bruni
Sara
S
Treves
Cristina
C
d'Albasio
Giuseppe
G
Bagnoli
Siro
S
Bonanomi
Andrea G
AG
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
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