Bacterial toxins impair functioning of Vit D3 and its receptor!!

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this one is written in complicated language, but basically saying that presence of bacterial toxins results in reduced/impaired functioning of vitamin D3 and of its receptor. Cell Immunol. 2004 Nov-Dec;232(1-2):137-43. Lipopolysaccharide

negatively modulates vitamin D action by down-regulating expression of

vitamin D-induced VDR in human monocytic THP-1 cells.Pramanik R...Litholink Corporation, 2250 W. Park Drive, Chicago, IL, USA. rpramanik@...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, 1alpha,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.PMID: 15876428 [PubMed - indexed for MEDLINE]