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

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• 作者：Tanupriya Agrawal ; Gaurav K. Gupta ; Devendra K. Agrawal ; ^{dkagr@creighton.edu}
• 关键词：AHR ; Airway hyperresponsiveness ; HBSMC ; Human bronchial smooth muscle cell ; PHB ; Prohibitin ; TNF-伪 ; Tumor necrosis factor-伪 ; VDR ; Vitamin D receptor
• 刊名：Experimental and Molecular Pathology
• 出版年：2012
• 期刊代码：291_00144800
• 类别：med
• 出版时间：August, 2012
• 卷：93
• 期：1
• 页码：74-81
• 文件大小：1392 K

摘要

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-伪. 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 2000 IU/kg of vitamin D-supplemented diet for 13 weeks. Mouse model of allergic airway inflammation was developed by OVA-sensitization and challenge. The expression pattern of TNF-伪, prohibitin and VDR in the lung of OVA-sensitized mice was analyzed using immunofluorescence. Calcitriol significantly increased and TNF-伪 decreased the protein and mRNA expression of prohibitin and VDR in HBSMCs. There was significantly increased expression of TNF-伪 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-伪, thereby increasing inflammation and decreases the expression of VDR and prohibitin. Supplementation with vitamin D might reduce the levels of TNF-伪, thereby increasing the expression of VDR and prohibitin that could be responsible for reducing allergic airway inflammation.