The Antiproliferative Effect of Calcitriol on Human Peripheral Blood Mononuclear Cells*

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Abstract
Activation of lymphocytes leads to the expression of receptors for the calcitropic hormone calcitriol [1,25(OH)2D3], and calcitriol is a potent inhibitor of interleukin– 2 (IL–2) and of lymphocyte proliferation. We used peripheral blood mononuclear cells (PBM) activated in vitro with phytohemagglutinin to study 1) the relationship between 1,25(OH)2D3 receptor expression, IL–2 production, and l,25(OH)2D3–induced inhibition of PBM proliferation in connection with the cell cycle; 2) the effect of 1,25(OH)2D3 on PBM activation and on the expression of activation–related molecules including the IL–2 receptor, and 3) the role of calcium in the antiproliferative effect of the hormone. 1,25(OH)2D3 receptor expression occurred when PBM entered the Gla phase of the cell cycle. The concentrationof the receptor protein reached a peak at G1b and declinedduring the S phase. 1,25(OH)2D3 inhibited cell proliferation by blocking PBM at the Gla–Glb border. The antiproliferative effect of calcitriol was not caused by hormonal interference with the calcium–dependent activation process nor with the expression of activation–related molecules including the IL–2 receptor. Moreover, this effect was not influenced by extracellular calcium, suggesting that the hormonal action cannot be due to calcium translocation. These findings support the contention that l,25(OH)2D3–induced inhibition of PBM proliferation is mediated through selective inhibition of IL–2 production.

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