Vitamin D deficiency decreases the expression of VDR and prohibitin in the lungs of mice with allergic airway inflammation.

Abstract

AIMS:

Asthma is one of the most common chronic inflammatory diseases of the airways. Calcitriol exerts its action through Vitamin D receptor (VDR), which is a high affinity nuclear receptor. VDR is a transcription factor that alters the transcription of target genes which are involved in a wide spectrum of biological responses. Lower serum vitamin D levels are associated with airway hyperresponsiveness and increased asthma severity. Prohibitin is a ubiquitously expressed protein localized to the cell and mitochondrial membranes and the nucleus.

METHODS AND RESULTS:

HBSMCs were cultured and treated with calcitriol and/or TNF-α. The mRNA and protein expression of prohibitin and VDR were analyzed using qPCR and immunoblotting, respectively. In the in vivo studies, female BALB/c mice were fed with special vitamin D-deficient or 2000IU/kg of vitamin D-supplemented diet for 13weeks. Mouse model of allergic airway inflammation was developed by OVA-sensitization and challenge. The expression pattern of TNF-α, prohibitin and VDR in the lung of OVA-sensitized mice was analyzed using immunofluorescence. Calcitriol significantly increased and TNF-α decreased the protein and mRNA expression of prohibitin and VDR in HBSMCs. There was significantly increased expression of TNF-α and decreased expression of VDR and prohibitin in the lung of vitamin D-deficient mouse model of allergic airway inflammation.

CONCLUSION:

These results suggest that under inflammatory conditions there is decreased expression of VDR resulting in decreased expression of prohibitin, which is a vitamin D target gene. Vitamin D deficiency causes increase in the expression of TNF-α, thereby increasing inflammation and decreases the expression of VDR and prohibitin. Supplementation with vitamin D might reduce the levels of TNF-α, thereby increasing the expression of VDR and prohibitin that could be responsible for reducing allergic airway inflammation.

• Authors: Tanupriya Agrawal, Gaurav K Gupta, Devendra K Agrawal
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 93 Issue 1 Pg. 74-81 (Aug 2012) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 22537547 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Prohibitins
• Receptors, Calcitriol
• Repressor Proteins
• Tumor Necrosis Factor-alpha
• Calcitriol

Topics

• Animals
• Asthma (metabolism)
• Bronchi (metabolism)
• Calcitriol (pharmacology)
• Cells, Cultured
• Female
• Humans
• Lung (drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Myocytes, Smooth Muscle (metabolism)
• Prohibitins
• Receptors, Calcitriol (biosynthesis)
• Repressor Proteins (biosynthesis)
• Tumor Necrosis Factor-alpha (biosynthesis, pharmacology)
• Vitamin D Deficiency (metabolism)