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

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 1,25(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 G1a phase of the cell cycle. The concentration of the receptor protein reached a peak at G1b and declined during the S phase. 1,25(OH)2D3 inhibited cell proliferation by blocking PBM at the G1a-G1b 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 1,25(OH)2D3-induced inhibition of PBM proliferation is mediated through selective inhibition of IL-2 production.

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

“…1,25(OH) 2 D 3 has also been demonstrated to stimulate T-suppressor-cell function, in vivo as well as in vitro (22,23), and is known to inhibit both T-and B-lymphocyte proliferation (24±26) as well as immunoglobulin production (25). 1,25(OH) 2 D 3 also inhibits the production of the growth-promoting lymphokine IL-2 (24,27,28), which was discovered to be the mechanism mediating the inhibition of lymphocyte proliferation (26,29). Activated T lymphocytes can serve as direct targets for 1,25(OH) 2 D 3 (30,31), but the effects of 1,25(OH) 2 D 3 on these cells are also the result of its actions on monocytes and macrophages in their role as APCs (32).…”

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

“…Vitamin D receptor gene is up-regulated during inflammation in endothelial cells [228][229] and vitamin D analogues protect against advanced glycation products derived insults [230]. Enriched vitamin D diet models promote anti-lymphoproliferative effect for the endothelium and a diminished response to inflammatory cytokines [231][232][233]. Moreover, as previously described, vitamin D regulates the expression of 74 genes and 36 proteins, connected with the correct development of the cytoskeleton and exerting a regulation on post-transcriptional controls for L-type voltage sensitive calcium channels [234][235][236].…”

Reconsidering the connection between vitamin D levels and age-related macular degeneration

“…[11][12][13][14]16 Evidence of inflammatory cell involvement in the later stages of AMD includes the presence of multinucleated giant cells and leukocytes in the choroid of AMD eyes 15 and in excised choroidal neovascularization. 20,22 A number of in vitro and in vivo studies have suggested an anti-inflammatory role for vitamin D. 23,24 It was also shown that vitamin D reduces the proliferation of cells of the immune system, [25][26][27][28][29] and that there is an inverse relationship between vitamin D levels and several chronic conditions associated with inflammation. [30][31][32][33] Owing to the potential causative role of inflammation in AMD development and progression, it is possible that vitamin D may protect against the occurrence and progression of AMD by virtue of its anti-inflammatory properties.…”