Vitamin D derivatives induce apoptosis and downregulate ICAM-1 levels in peripheral blood mononuclear cells of inflammatory bowel disease patients
✍ Scribed by Maria Martinesi; Cristina Treves; Giuseppe d'Albasio; Siro Bagnoli; Andrea G. Bonanomi; Maria Stio
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 366 KB
- Volume
- 14
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
Background:
Lymphocytes are crucial in the pathogenesis of inflammatory bowel disease (ibd) and are an important target for drug development. our aim was to verify whether 2 vitamin d derivatives, 1,25-dihydroxyvitamin d3 [1,25(oh)2d3] and eb 1089, could induce cell apoptosis and affect cell-cell interaction by regulating adhesion molecule levels.
Methods:
Peripheral blood mononuclear cell (pbmc) proliferation was studied by [3h]thymidine incorporation and apoptosis was determined using an enzyme-linked immunosorbent assay (elisa) kit. (poly(adp-ribose)polymerase (parp) cleavage, caspase-3, and icam-1 protein levels were determined by western blot analysis.
Results:
Our results indicate that 1,25(oh)2d3 or eb 1089 or anti-tnf-alpha (infliximab) induce apoptosis in pbmc obtained from healthy subjects. in ibd patients apoptosis is induced by vitamin d derivatives and by anti-tnf-alpha only in cd patients. caspase-3 activation and parp cleavage are registered when pbmc were treated with vitamin d derivatives. icam-1 levels remarkably increase when pbmc was incubated with lipopolysaccharide (lps) or tnf-alpha. the treatment with the vitamin d derivatives, alone or in combination with lps or tnf-alpha, significantly decreases icam-1 levels both in healthy subjects and ibd patients. in huvec cocultured with pbmc, previously incubated with lps or tnf-alpha associated with 1,25(oh)2d3, icam-1 levels decrease both in healthy subjects and ibd patients.
Conclusions:
1,25(oh)2d3 and eb 1089 inhibit pbmc proliferation, induce apoptosis in pbmc of healthy subjects and ibd patients, and affect icam-1 expression on pbmc and on huvec cocultured with pbmc, suggesting that the icam-1 downregulation could provide a new target for controlling the recruitment of leukocytes at the sites of inflammation in ibd.