Regulation of 1α,25‐dihydroxyvitamin D3 synthesis in macrophages from arthritic joints by phorbol ester, dibutyryl‐cAMP and calcium ionophore (A23187)

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Abstract
Phorbol 12-myristate 13-acetate (100 nM), a potent protein kinase C and macrophage activator, has a biphasic affect on 25(OH)D3-1α-hydroxylase activity in synovial fluid macrophages from arthritis patients, After 5 h, 1α,25(OH)D3 synthesis fell from 5.2 ± 0.1 to 1.6 ± 0.2 pmol/h per 106 cells, however, after 24 h and 48 h, synthesis increased to 17.4 ± 0.3 and 22.3 ± 1.4 pmol/h per 106 cells, respectively. Although an independent short-term mechanism is suggested, protein kinase C may promote macrophage activation, thus increasing long-term 25(OH)D3-1α-hydroxylase expression. Intracellular calcium and cAMP are unlikely to activate the enzyme, since 0.1 μM of the calcium ionophore, A23187, and 1 mM dibutyryl-cAMP inhibited synthesis by 87% and 79%, respectively, after 24 h.