1,25-Dihydroxyvitamin D3 and Adenosine 3’,5’-Monophosphate Synergistically Promote Differentiation of a Monocytic Cell Line*

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Abstract
CAMP and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have both been shown to affect cell proliferation and phenotype. Since 1,25-(OH)2D3 modulates cellular cAMP production in the U937 cell line, we have investigated the possibility that 1,25-(OH)2D3 may interact with cAMP to affect distal cellular events. The U937 cell normally contains less than 2000 receptors/cell for the chemotactic factor C5a, as measured by concentration-dependent binding assays with the ligand probe [125I]iodo-C5a; this number rises when the cell is exposed to agents that promote cellular differentiation, such as (Bu)2cAMP. U937 cells incubated with 1,25-(OH)2D3 or cAMP agonists [prostaglandin (0.03-3 .mu.M), isoproterenol (10-7-10-5 M), and forskolin (5-15 .mu.M)] alone demonstrate no increase in C5a receptor number. When the cAMP agonists are combined with 1,25-(OH)2D3 for up to 4 days, receptors are induced to levels comparable to those achieved with pharmacological doses of (Bu)2cAMP (25,000-75,000/cell), with a similar dose inducing half-maximal binding of C5a (.apprx. 1-3 nM). The synergistic effects of 1,25-(OH)2D3 and cAMP agonists are dose and time dependent; other metabolites of vitamin D are not effective. The data suggest that 1,25-(OH)2D3 may facilitate the effects of endogenous cAMP to promote certain types of differentiation.

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