1,25-dihydroxyvitamin D3 and agents that increase intracellular adenosine 3',5'-monophosphate synergistically inhibit the mitogenic stimulation of human lymphocytes.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], like the immune response modulators prostaglandin E2 (PGE2) and histamine, inhibits mitogen-induced proliferation of human peripheral blood mononuclear cells. 1,25-(OH)2D3 acts synergistically with PGE2 and histamine to inhibit lymphocyte mitogenesis. This is apparent at a wide concentration range of 1,25-(OH)2D3 (3 X 10(-11)-10(-8) mol/L). Cholera toxin, forskolin, and isobutylmethylxanthine, which like PGE2 and histamine increase intracellular concentrations of cAMP, also act synergistically with 1,25-(OH)2D3 in this system. Culture of mitogen-stimulated adherent cell-depleted mononuclear cells with PGE2 increases the number of high affinity binding sites for 1,25-(OH)2D3. This finding may account for the synergistic interaction between the two agents.
Rogoff Medical Research Institute, Petah Tikva, Israel.
A
A
Ravid
R
R
Koren
R
R
Narinsky
C
C
Rotem
A
A
Novogrodsky
A
A
Liberman
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000096:biosynthesis*; D001665:Binding Sites / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*
D005576:Colforsin; D000249:Adenosine Monophosphate; D006632:Histamine; D002772:Cholera Toxin; D000242:Cyclic AMP; D002117:Calcitriol; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine