Effects of human interleukins in the transgenic gene reporter cell lines IZ-VDRE and IZ-CYP24 designed to assess the transcriptional activity of vitamin D receptor

PLoS One. 2018 Feb 28;13(2):e0193655. doi: 10.1371/journal.pone.0193655. eCollection 2018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Cell Line
  • Genes, Reporter / genetics*
  • Humans
  • Interleukins / pharmacology*
  • Receptors, Calcitriol / genetics*
  • Transcription, Genetic / drug effects*
  • Transfection
  • Transgenes / genetics*
  • Vitamin D3 24-Hydroxylase / genetics

Substances

  • Interleukins
  • Receptors, Calcitriol
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Grants and funding

Our laboratory is supported by a grant from the Czech Science Foundation GACR P303/12/G163, by the student grants from Palacky University (Grant no. PrF-2017-004 and No. PrF-2018-005) and by the Operational Programme Research, Development and Education Regional Development Fund, project no. CZ.02.1.01/0.0/0.0/16_019/0000754 of the Ministry of Education, Youth and Sports of the Czech Republic (all received by Zdenek Dvorak).