title: Vitamin D deficiency decreases the expression of VDR and prohibitin in the lungs of mice with allergic airway inflammation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Biomedical Sciences and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Tanupriya
authors.initials: T
authors.lastname: Agrawal
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Gupta
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D000091402:Prohibitins; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism*
chemical_list: D000091402:Prohibitins; D018167:Receptors, Calcitriol; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol