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.

Department of Cell Biology and Genetics Faculty of Science Palacky University Olomouc Czech Republic

Department of Pathophysiology and Allergy Research Medical University of Vienna Vienna Austria

Zobrazit více v PubMed

Tsoukas CD, Provvedini DM, Manolagas SC. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science, 1984. 224(4656): p. 1438–40. PubMed

Wobke TK, Sorg BL Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol, 2014. 5: p. 244 doi: 10.3389/fphys.2014.00244 PubMed DOI PMC

Marcotorchino J, Gouranton E, Romier B, Tourniaire F, Astier J, Malezet C, et al. Vitamin D reduces the inflammatory response and restores glucose uptake in adipocytes. Mol Nutr Food Res, 2012. 56(12): p. 1771–82. doi: 10.1002/mnfr.201200383 PubMed DOI

Rostkowska-Nadolska B, Sliupkas-Dyrda E, Potyka J, Kusmierz D, Fraczek M, Krecicki T. et al. Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures. Adv Med Sci, 2010. 55(1): p. 86–92. doi: 10.2478/v10039-010-0012-9 PubMed DOI

Bhalla AK, Amento EP, Krane SM. Differential effects of 1,25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: inhibition of interleukin-2 and augmentation of interleukin-1 production. Cell Immunol, 1986. 98(2): p. 311–22. PubMed

Hummel DM, Fetahu IS, Groschel C, Manhardt T, Kallay E. Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells. J Steroid Biochem Mol Biol, 2014. 144 Pt A: p. 91–5. doi: 10.1016/j.jsbmb.2013.09.017 PubMed DOI PMC

Schrumpf JA, van Sterkenburg MA, Verhoosel RM, Zuyrderduyn S, Hiemstra PS. Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells. Infect Immun, 2012. 80(12): p. 4485–94. doi: 10.1128/IAI.06224-11 PubMed DOI PMC

Bartonkova I, Grycova A, Dvorak Z. Profiling of Vitamin D Metabolic Intermediates toward VDR Using Novel Stable Gene Reporter Cell Lines IZ-VDRE and IZ-CYP24. Chem Res Toxicol, 2016. 29(7): p. 1211–22. doi: 10.1021/acs.chemrestox.6b00170 PubMed DOI

Biola A, Lefebvre P, Perrin-Wolff M, Sturm M, Bertoglio J, Pallardy M. Interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving STAT5 (signal transducer and activator of transcription 5) but not AP-1. Mol Endocrinol, 2001. 15(7): p. 1062–76. doi: 10.1210/mend.15.7.0657 PubMed DOI

Pace TW, Hu F, Miller AH. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun, 2007. 21(1): p. 9–19. doi: 10.1016/j.bbi.2006.08.009 PubMed DOI PMC

Miller AH, Pariante CM, Pearce BD. Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistance and relevance to depression. Adv Exp Med Biol, 1999. 461: p. 107–16. doi: 10.1007/978-0-585-37970-8_7 PubMed DOI

Hobisch A, Eder IE, Putz T, Horninger W, Bartsch G, Klocker H et al. Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res, 1998. 58(20): p. 4640–5. PubMed

Lin DL, Whitney MC, Yao Z, Keller ET. Interleukin-6 induces androgen responsiveness in prostate cancer cells through up-regulation of androgen receptor expression. Clin Cancer Res, 2001. 7(6): p. 1773–81. PubMed

Ueda T, Mawji NR, Bruchovsky N, Sadar MD. Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells. J Biol Chem, 2002. 277(41): p. 38087–94. doi: 10.1074/jbc.M203313200 PubMed DOI

Yang L, Wang L, Lin HK, Kan PY, Xie S, Tsai MY, et al. Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells. Biochem Biophys Res Commun, 2003. 305(3): p. 462–9. PubMed

Pascussi JM, Gerbal-Chaloin S, Pichard-Garcia L, Daujat M, Fabre JM, Maurel P, et al. Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes. Biochem Biophys Res Commun, 2000. 274(3): p. 707–13. doi: 10.1006/bbrc.2000.3219 PubMed DOI

Axen E, Postlind H, Wikvall K. Effects on CYP27 mRNA expression in rat kidney and liver by 1 alpha, 25-dihydroxyvitamin D3, a suppressor of renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity. Biochem Biophys Res Commun, 1995. 215(1): p. 136–41. doi: 10.1006/bbrc.1995.2443 PubMed DOI

Kallay E, Bises G, Bieglmayer C, Gerdenitsch W, Steffan I, et al. Colon-specific regulation of vitamin D hydroxylases—a possible approach for tumor prevention. Carcinogenesis, 2005. 26(9): p. 1581–9. doi: 10.1093/carcin/bgi124 PubMed DOI

Cross HS, Nittke T, Kallay E.,Colonic vitamin D metabolism: implications for the pathogenesis of inflammatory bowel disease and colorectal cancer. Mol Cell Endocrinol, 2011. 347(1–2): p. 70–9. doi: 10.1016/j.mce.2011.07.022 PubMed DOI

Hii CS, Ferrante A,The Non-Genomic Actions of Vitamin D. Nutrients, 2016. 8(3): p. 135 doi: 10.3390/nu8030135 PubMed DOI PMC

Pascussi JM, Gerbal-Chaloin S, Duret C, Daujat-Chavanieu M, Vilarem MJ, Maurel P. The tangle of nuclear receptors that controls xenobiotic metabolism and transport: crosstalk and consequences. Annu Rev Pharmacol Toxicol, 2008. 48: p. 1–32. doi: 10.1146/annurev.pharmtox.47.120505.105349 PubMed DOI

Pascussi JM, Robert A, Nguyen M, Walrant-Debray O, Garabedian M, Martin P, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest, 2005. 115(1): p. 177–86. doi: 10.1172/JCI21867 PubMed DOI PMC