Suppressive effect of 1,25-dihydroxyvitamin D3 and its analogues EB 1089 and KH 1060 on T lymphocyte proliferation in active ulcerative colitis.
This study examined the effect exerted by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and two vitamin D analogues, EB 1089 and KH 1060, on the proliferation of T lymphocytes obtained from ulcerative colitis (UC) patients and healthy controls. The proliferative response of T lymphocytes to phytohaemagglutinin treatment was first analyzed on days three, five, and seven of culture. Cell proliferation was significantly lower in UC patients than that observed in healthy controls. The highest proliferation value, in either controls or patients, was registered on day five of culture. On day seven, a decrease in proliferation occurred, less evident in patients with respect to controls, whereas on day three, controls and patients showed the same proliferation value. The response of T lymphocytes of either healthy controls or UC patients to 1,25(OH)2D3, EB 1089, or KH 1060 was then investigated, treating the cells for three, five, and seven days with 10 nM vitamin D derivatives. In the presence of these compounds, cell proliferation was significantly inhibited in both groups, but on day seven, the inhibition of lymphocyte proliferation was remarkable in controls, whereas in patients it was similar to that registered on day five. The highest inhibition values were always obtained in the presence of KH 1060, and the time dependence was continuous in controls, but in the presence of EB 1089 only in patients. T lymphocytes prepared from healthy controls and UC patients were then cultured for five days in the presence of vitamin D derivatives at three different concentrations (0.1, 1, and 10 nM). In the two groups, a dose-dependent inhibition was registered in the presence of 1,25(OH)2D3 or EB 1089, while the inhibition of proliferation exerted by KH 1060 was not dose-dependent. The results obtained suggest an option for the use of the two non-hypercalcemic vitamin D analogues in the therapy of UC patients, perhaps in association with other immunosuppressive drugs.
Stio
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M
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy. maria.stio@unifi.it
Bonanomi
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AG
d'Albasio
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Treves
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D000328:Adult; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002120:Calcium Channel Agonists; D002455:Cell Division / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D002120:Calcium Channel Agonists; D007166:Immunosuppressive Agents; D008934:Mitogens; C074279:KH 1060; D002117:Calcitriol; C078903:seocalcitol