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Journal of Clinical Immunology

Erschienen in:

01.07.2009

Plasma 1,25 Dihydroxy Vitamin D₃ Level and Expression of Vitamin D Receptor and Cathelicidin in Pulmonary Tuberculosis

verfasst von: P. Selvaraj, S. Prabhu Anand, M. Harishankar, K. Alagarasu

Erschienen in: Journal of Clinical Immunology | Ausgabe 4/2009

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Abstract

Introduction

Vitamin D₃, which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations between low serum vitamin D₃ levels and increased risk of tuberculosis have been reported.

Study Subjects and Methods

Plasma 1,25 dihydroxy vitamin D₃ levels (1,25(OH)₂ D₃) and ex vivo levels of VDR protein from peripheral blood mononuclear cells were studied in 65 pulmonary tuberculosis (PTB) patients and 60 normal healthy subjects (NHS) using enzyme-linked immunosorbent assay-based methods. Using real-time polymerase chain reaction (PCR), induction of VDR, cathelicidin, and CYP27B1 mRNA were studied in live Mycobacterium tuberculosis-stimulated macrophage cultures treated with or without 1,25 dihydroxy vitamin D₃. VDR and CYP27B1 (-1077 A/T) gene polymorphisms were studied using PCR-based methods.

Results

1,25(OH)₂ D₃ were significantly increased (p = 0.0004), while ex vivo levels of VDR protein were significantly decreased in PTB patients (p = 0.017) as compared to NHS. 1,25(OH)₂ D₃ levels were not different between variant genotypes of CYP27B1. A trend towards decreased levels of VDR protein was observed among NHS with BsmI BB and TaqI tt genotypes compared to NHS with other genotypes. Relative quantification of mRNA using real-time PCR revealed increased VDR mRNA expression in live M. tuberculosis-stimulated culture in PTB patients (p < 0.01) than normal healthy subjects. Cathelicidin mRNA expression was significantly increased in vitamin D₃-treated cultures compared to unstimulated and M. tuberculosis-stimulated culture in both patients (p < 0.001) and NHS (p < 0.05).

Conclusions

The present study suggests that PTB patients may have increased 1,25(OH)₂ D₃ levels, and this might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling. Moreover, addition of 1,25(OH)₂ D₃ might lead to increased expression of cathelicidin which could enhance the immunity against tuberculosis.

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Titel: Plasma 1,25 Dihydroxy Vitamin D3 Level and Expression of Vitamin D Receptor and Cathelicidin in Pulmonary Tuberculosis
verfasst von: P. Selvaraj
S. Prabhu Anand
M. Harishankar
K. Alagarasu
Publikationsdatum: 01.07.2009
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 4/2009
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-009-9277-9

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Abstract

Introduction

Study Subjects and Methods

Results

Conclusions

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