Abstract
The role of vitamin D receptor (VDR) in immune responses has been broadly studied and it has been shown that activated VDR alters the levels of some interleukins (ILs). In this study, we studied the opposite, i.e. whether 13 selected pro-inflammatory and anti-inflammatory ILs influence the transcriptional activity of human VDR. The experimental models of choice were two human stably transfected gene reporter cell lines IZ-VDRE and IZ-CYP24, which were designed to evaluate the transcriptional activity of VDR. The gene reporter assays revealed inhibition of calcitriol-induced luciferase activity by IL-4 and IL-13, when 1 ng/mL of these two compounds decreased the effect of calcitriol down to 60% of the control value. Consistently, calcitriol-induced expression of CYP24A1 mRNA was also significantly decreased by IL-4 and IL-13. The expression of VDR and CYP27B1 mRNAs was not influenced by any of the 13 tested ILs. These data suggest possible cross-talk between the VDR signalling pathway and IL-4- and IL-13-mediated cell signalling.
Highlights
Vitamin D receptor (VDR) is an essential regulator of calcium homeostasis and bone metabolism
Prior to the gene reporter assays, we examined the effect of ILs on the viability of IZ-CYP24 and IZ-VDRE cells
We measured the catalytic activity of NanoLuciferase in IZ-CYP24 and IZ-VDRE cells in the presence or absence of the test ILs
Summary
Vitamin D receptor (VDR) is an essential regulator of calcium homeostasis and bone metabolism. It has been shown that calcitriol (one of the D vitamins) plays crucial roles in other physiological processes including in the induction of cell differentiation, inhibition of cell proliferation, modulation of the immune system and control of other hormonal systems. The identification of compounds, endogenous or synthetic, that alter the transcriptional activation of VDR is highly relevant. Modulation of immune responses by VDR has been extensively studied during past decades. Interleukins (ILs) are a group of cytokines that are involved in the communication between immune and inflammatory cells, and 38 ILs have been identified far.
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