Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the mechanisms of 1,25-dihydroxyvitamin D3 (D3)-mediated inhibition of human B cell differentiation to immunoglobulin (Ig) secreting cells. B lymphocytes were purified from human tonsils and peripheral blood mononuclear cells. Mononuclear cells were separated into adherent cells and nonadherent cells. Cells were stimulated with Staphylococcus aureus Cowen I (SAC) or pokeweed mitogen (PWM) for 7 days and immunoglobulin production was measured by ELISA assay, 1,25-dihydroxyvitamin D3 was added at different times during cultures. 1,25-Dihydroxyvitamin D3, in a dose-dependent manner, inhibited both SAC and PWM-induced Ig production by mononuclear cells. The maximum inhibition was observed when 1,25-dihydroxyvitamin D3 was added at the beginning of culture, but inhibition could still be observed when 1,25-dihydroxyvitamin D3 was added on day 4 of cultures. The inhibitory effect of 1,25-dihydroxyvitamin D3 on Ig production was significantly greater on mononuclear cells than on nonadherent cells. Addition of in vitro purified IL-1 to nonadherent cells enhanced 1,25-dihydroxyvitamin D3-induced inhibition of Ig production. 1,25-Dihydroxyvitamin D3 also inhibited the expression of IL-2 receptors on B cells activated with SAC. 1,25-dihydroxyvitamin D3 did not inhibit Ig production by SAC preactivated B cell blasts in response to T cell supernatants. These data suggest that vitamin D3 inhibits Ig production by inhibiting IL-2 receptor expression on B cells and via its effect on adherent macrophages. Vitamin D3 does not influence the effect of differentiation factors on activated B cells that have already expressed growth/differentiation factor receptors.
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PMID:1,25-Dihydroxyvitamin D3-mediated inhibition of human B cell differentiation. 311 62

Sarcoidosis is characterized by the accumulation of activated lymphocytes in the lungs and other organs and by the spontaneous production of the active form of vitamin D, calcitriol. We hypothesized that calcitriol may modulate the responsiveness of human lymphocytes to the relevant biologic mediator, interleukin-2 (IL-2). After culture for 48 h with phytohemagglutinin, human peripheral blood lymphocytes migrated through nitrocellulose filters, secured in microchemotaxis chambers, in response to IL-2. When calcitriol at 1 nM was included in the cultures, the migratory response to IL-2 was completely abrogated. This inhibitory effect was seen despite the fact that cultured lymphocytes continued to express the IL-2 receptor and other activation markers. A similar but more rapid effect could be demonstrated by including calcitriol in the lower well during our 3-h chemokinesis assay. Calcitriol blocked IL-2-induced lymphocyte migration in a dose-dependent fashion. The synthetic noncalcemic vitamin D analogue MC 903 was equally effective in this assay. IL-2-induced migration could also be prevented by the protein kinase C inhibitor H-7, but calcitriol appeared to be at least 1,000 times more potent. Our studies suggest that calcitriol is a potent natural immunomodulator with rapid suppressive effects that may be mediated through protein kinase C. Synthetic analogues such as MC 903 may offer exciting therapeutic opportunities.
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PMID:Calcitriol and its synthetic analogue MC 903 inhibit the interleukin-2-induced migration of human lymphocytes. 776 30

1,25-Dihydroxycholecalciferol [1,25(OH)2D], besides its role in calcium and phosphorus homeostasis, is also an important immunoregulatory molecule. Plasma levels of this hormone may be normal or elevated in patients with primary hyperparathyroidism. 1,25(OH)2D has been reported to inhibit production of the cytokines interleukin-2 (IL-2) and IL-6. In the present study, we examined the effect of parathyroid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by peripheral blood lymphocytes (each measurement was performed twice). Ten patients (5 females and 5 males aged 45 to 78 years) with primary hyperparathyroidism were enrolled in the study. The diagnosis of primary hyperparathyroidism was based on the presence of asymptomatic hypercalcemia, hypophosphatemia, and elevated serum intact PTH levels. Three weeks after removal of the parathyroid adenoma, there was a significant increase in the serum level of IL-2R, as well as the PHA-stimulated peripheral blood lymphocyte production of IL-6 and release of IL-2R. The results indicate that the removal of a parathyroid adenoma in patients with primary hyperparathyroidism causes a significant increase in IL-2R and IL-6 levels. The mechanism by which hyperparathyroidism may affect these cytokines and how they seem related to the levels of vitamin D is discussed.
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PMID:Effect of parathyroid adenoma excision on interleukin-6 (IL-6) and IL-2 receptor levels. 1069 Sep 43