Lipopolysaccharide negatively modulates vitamin D action by down-regulating expression of vitamin D-induced VDR in human monocytic THP-1 cells

Rocky Pramanik, John R. Asplin, Christina Lindeman, Murray J. Favus, Shaochun Bai, Fredric L. Coe

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Vitamin D3, an important seco-steroid hormone for the regulation of body calcium homeostasis, promotes immature myeloid precursor cells to differentiate into monocytes/macrophages. Vitamin D receptor (VDR) belongs to a nuclear receptor super-family that mediates the genomic actions of vitamin D3 and regulates gene expression by binding with vitamin D response elements in the promoter region of the cognate gene. Thus by regulating gene expression, VDR plays an important role in modulating cellular events such as differentiation, apoptosis, and growth. Here we report lipopolysaccharide (LPS), a bacterial toxin; decreases VDR protein levels and thus inhibits VDR functions in the human blood monocytic cell line, THP-1. The biologically active form of vitamin D3, 1α,25-dihydroxy vitamin D3 [1,25(OH)2D3], induced VDR in THP-1 cells after 24 h treatment, and LPS inhibited 1,25(OH)2D3-mediated VDR induction. However, LPS and 1,25(OH)2D3 both increased VDR mRNA levels in THP-1 cells 20 h after treatment, as observed by real time RT-PCR. Moreover, LPS plus 1,25(OH)2D3 action on VDR mRNA level was additive and synergistic. A time course experiment up to 60 h showed an increase in VDR mRNA that was not preceded with an increase in VDR protein levels. Although the proteasome pathway plays an important role in VDR degradation, the proteasome inhibitor lactacystin had no effect on the LPS-mediated down-regulation of 1,25(OH)2D3 induced VDR levels. Reduced VDR levels by LPS were accompanied by decreased 1,25(OH) 2D3/VDR function determined by VDR responsive 24-hydroxylase (CYP24) gene expression. The above results suggest that LPS impairs 1,25(OH)2D3/VDR functions, which may negatively affect the ability of 1,25(OH)2D3 to induce myeloid differentiation into monocytes/macrophages.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalCellular Immunology
Volume232
Issue number1-2
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Calcitriol Receptors
Vitamin D
Lipopolysaccharides
Cholecalciferol
Gene Expression
Messenger RNA
Monocytes
Vitamin D Response Element
Macrophages
Bacterial Toxins
Proteasome Inhibitors
Myeloid Cells
Proteasome Endopeptidase Complex
Cytoplasmic and Nuclear Receptors
Mixed Function Oxygenases

Keywords

  • 1,25(OH)D
  • CYP24
  • Lactacystin
  • LPS
  • Monocyte
  • THP-1
  • VDR
  • Vitamin D

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Lipopolysaccharide negatively modulates vitamin D action by down-regulating expression of vitamin D-induced VDR in human monocytic THP-1 cells. / Pramanik, Rocky; Asplin, John R.; Lindeman, Christina; Favus, Murray J.; Bai, Shaochun; Coe, Fredric L.

In: Cellular Immunology, Vol. 232, No. 1-2, 11.2004, p. 137-143.

Research output: Contribution to journalArticle

Pramanik, Rocky ; Asplin, John R. ; Lindeman, Christina ; Favus, Murray J. ; Bai, Shaochun ; Coe, Fredric L. / Lipopolysaccharide negatively modulates vitamin D action by down-regulating expression of vitamin D-induced VDR in human monocytic THP-1 cells. In: Cellular Immunology. 2004 ; Vol. 232, No. 1-2. pp. 137-143.
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