Regulation of 1 alpha, 25-dihydroxyvitamin D3 synthesis in macrophages from arthritic joints by phorbol ester, dibutyryl-cAMP and calcium ionophore (A23187).
Phorbol 12-myristate 13-acetate (100 nM), a potent protein kinase C and macrophage activator, has a biphasic affect on 25(OH)D3-1 alpha-hydroxylase activity in synovial fluid macrophages from arthritis patients. After 5 h, 1 alpha, 25(OH)D3 synthesis fell from 5.2 +/- 0.1 to 1.6 +/- 0.2 pmol/h per 10(6) cells, however, after 24 h and 48 h, synthesis increased to 17.4 +/- 0.3 and 22.3 +/- 1.4 pmol/h per 10(6) cells, respectively. Although an independent short-term mechanism is suggested, protein kinase C may promote macrophage activation, thus increasing long-term 25(OH)D3-1 alpha-hydroxylase expression. Intracellular calcium and cAMP are unlikely to activate the enzyme, since 0.1 microM of the calcium ionophore, A23187, and 1 mM dibutyryl-cAMP inhibited synthesis by 87% and 79%, respectively, after 24 h.
Yuan
J Y
JY
Manchester University Bone Disease Research Centre, Royal Infirmary, UK.
Freemont
A J
AJ
Mawer
E B
EB
Hayes
M E
ME
D001168:Arthritis / Q000378:metabolism*; D015210:Arthritis, Gouty / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000001:Calcimycin; D003994:Bucladesine; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate