Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells

Research output: Contribution to journalJournal articlepeer-review

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Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells. / Kongsbak, Martin; von Essen, Marina R; Boding, Lasse; Levring, Trine B; Schjerling, Peter; Lauritsen, Jens P H; Woetmann, Anders; Ødum, Niels; Bonefeld, Charlotte M; Geisler, Carsten.

In: PLOS ONE, Vol. 9, No. 5, e96695, 2014, p. 1-12.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Kongsbak, M, von Essen, MR, Boding, L, Levring, TB, Schjerling, P, Lauritsen, JPH, Woetmann, A, Ødum, N, Bonefeld, CM & Geisler, C 2014, 'Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells', PLOS ONE, vol. 9, no. 5, e96695, pp. 1-12. https://doi.org/10.1371/journal.pone.0096695

APA

Kongsbak, M., von Essen, M. R., Boding, L., Levring, T. B., Schjerling, P., Lauritsen, J. P. H., Woetmann, A., Ødum, N., Bonefeld, C. M., & Geisler, C. (2014). Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells. PLOS ONE, 9(5), 1-12. [e96695]. https://doi.org/10.1371/journal.pone.0096695

Vancouver

Kongsbak M, von Essen MR, Boding L, Levring TB, Schjerling P, Lauritsen JPH et al. Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells. PLOS ONE. 2014;9(5):1-12. e96695. https://doi.org/10.1371/journal.pone.0096695

Author

Kongsbak, Martin ; von Essen, Marina R ; Boding, Lasse ; Levring, Trine B ; Schjerling, Peter ; Lauritsen, Jens P H ; Woetmann, Anders ; Ødum, Niels ; Bonefeld, Charlotte M ; Geisler, Carsten. / Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells. In: PLOS ONE. 2014 ; Vol. 9, No. 5. pp. 1-12.

Bibtex

@article{e3c5d990af414c899fa32ae9e09f8312,
title = "Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells",
abstract = "The active form of vitamin D3, 1,25(OH)2D3, has significant immunomodulatory properties and is an important determinant in the differentiation of CD4+ effector T cells. The biological actions of 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR) and are believed to correlate with the VDR protein expression level in a given cell. The aim of this study was to determine if and how 1,25(OH)2D3 by itself regulates VDR expression in human CD4+ T cells. We found that activated CD4+ T cells have the capacity to convert the inactive 25(OH)D3 to the active 1,25(OH)2D3 that subsequently up-regulates VDR protein expression approximately 2-fold. 1,25(OH)2D3 does not increase VDR mRNA expression but increases the half-life of the VDR protein in activated CD4+ T cells. Furthermore, 1,25(OH)2D3 induces a significant intracellular redistribution of the VDR. We show that 1,25(OH)2D3 stabilizes the VDR by protecting it from proteasomal degradation. Finally, we demonstrate that proteasome inhibition leads to up-regulation of VDR protein expression and increases 1,25(OH)2D3-induced gene activation. In conclusion, our study shows that activated CD4+ T cells can produce 1,25(OH)2D3, and that 1,25(OH)2D3 induces a 2-fold up-regulation of the VDR protein expression in activated CD4+ T cells by protecting the VDR against proteasomal degradation.",
author = "Martin Kongsbak and {von Essen}, {Marina R} and Lasse Boding and Levring, {Trine B} and Peter Schjerling and Lauritsen, {Jens P H} and Anders Woetmann and Niels {\O}dum and Bonefeld, {Charlotte M} and Carsten Geisler",
year = "2014",
doi = "10.1371/journal.pone.0096695",
language = "English",
volume = "9",
pages = "1--12",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

RIS

TY - JOUR

T1 - Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells

AU - Kongsbak, Martin

AU - von Essen, Marina R

AU - Boding, Lasse

AU - Levring, Trine B

AU - Schjerling, Peter

AU - Lauritsen, Jens P H

AU - Woetmann, Anders

AU - Ødum, Niels

AU - Bonefeld, Charlotte M

AU - Geisler, Carsten

PY - 2014

Y1 - 2014

N2 - The active form of vitamin D3, 1,25(OH)2D3, has significant immunomodulatory properties and is an important determinant in the differentiation of CD4+ effector T cells. The biological actions of 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR) and are believed to correlate with the VDR protein expression level in a given cell. The aim of this study was to determine if and how 1,25(OH)2D3 by itself regulates VDR expression in human CD4+ T cells. We found that activated CD4+ T cells have the capacity to convert the inactive 25(OH)D3 to the active 1,25(OH)2D3 that subsequently up-regulates VDR protein expression approximately 2-fold. 1,25(OH)2D3 does not increase VDR mRNA expression but increases the half-life of the VDR protein in activated CD4+ T cells. Furthermore, 1,25(OH)2D3 induces a significant intracellular redistribution of the VDR. We show that 1,25(OH)2D3 stabilizes the VDR by protecting it from proteasomal degradation. Finally, we demonstrate that proteasome inhibition leads to up-regulation of VDR protein expression and increases 1,25(OH)2D3-induced gene activation. In conclusion, our study shows that activated CD4+ T cells can produce 1,25(OH)2D3, and that 1,25(OH)2D3 induces a 2-fold up-regulation of the VDR protein expression in activated CD4+ T cells by protecting the VDR against proteasomal degradation.

AB - The active form of vitamin D3, 1,25(OH)2D3, has significant immunomodulatory properties and is an important determinant in the differentiation of CD4+ effector T cells. The biological actions of 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR) and are believed to correlate with the VDR protein expression level in a given cell. The aim of this study was to determine if and how 1,25(OH)2D3 by itself regulates VDR expression in human CD4+ T cells. We found that activated CD4+ T cells have the capacity to convert the inactive 25(OH)D3 to the active 1,25(OH)2D3 that subsequently up-regulates VDR protein expression approximately 2-fold. 1,25(OH)2D3 does not increase VDR mRNA expression but increases the half-life of the VDR protein in activated CD4+ T cells. Furthermore, 1,25(OH)2D3 induces a significant intracellular redistribution of the VDR. We show that 1,25(OH)2D3 stabilizes the VDR by protecting it from proteasomal degradation. Finally, we demonstrate that proteasome inhibition leads to up-regulation of VDR protein expression and increases 1,25(OH)2D3-induced gene activation. In conclusion, our study shows that activated CD4+ T cells can produce 1,25(OH)2D3, and that 1,25(OH)2D3 induces a 2-fold up-regulation of the VDR protein expression in activated CD4+ T cells by protecting the VDR against proteasomal degradation.

U2 - 10.1371/journal.pone.0096695

DO - 10.1371/journal.pone.0096695

M3 - Journal article

C2 - 24792400

VL - 9

SP - 1

EP - 12

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - e96695

ER -

ID: 117551908