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

FEBS Letters

Hayes, M.E.²  Freemont, A.J.¹  Mawer, E.B.²  Yuan, J.Y.² 

[1] Rheumatology, Stopford Building, Oxford Road, Manchester, UK;Manchester University Bone Disease Research Centre and University Departments of Medicine, The Royal Infirmary, Stopford Building, Oxford Road, Manchester, UK

关键词: Macrophage;    1α;    25-(OH)2D3;    Inflammatory arthritis;    Phorbol ester;    Cyclic AMP;    Calcium ionophore A23187;    25(OH)D3;    25-hydroxyvitamin D3;    1α;    25(OH)2D3;    1α;    25-dihydroxyvitamin D3;    24;    25(OH)2D3;    24;    25-dihydroxyvitamin D3;    cAMP;    cyclic adenosine monophosphate;    Mø;    macrophage;    IFN-γ;    interferon-gamma;    TNF-α;    tumour necrosis factor-alpha;    LPS;    bacterial lipopolysaccharide;    PMA;    phorbol 12-myristate 13-acetate;    PKC;    potent protein kinase C;    Cai;    intracellular calcium;   

DOI  :  10.1016/0014-5793(92)81370-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown