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

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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Acknowledgments

We acknowledge the Council of Scientific and Industrial Research, New Delhi for providing senior research fellowship to Mr. S. Prabhu Anand and Indian Council of Medical Research, New Delhi for providing senior research fellowship to Mr. K. Alagarasu. The help rendered by clinician Dr. N. Meenakshi and staffs, namely Mrs. Kasturi Sasikumar and Mrs. Thilagavathi of Government Thiruvotteeswarar hospital of Thoracic medicine (GTHTM) and staffs of Institute of Thoracic medicine (ITM), Chennai for their kind assistance in obtaining the blood samples, is acknowledged.

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Correspondence to P. Selvaraj.

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Selvaraj, P., Prabhu Anand, S., Harishankar, M. et al. Plasma 1,25 Dihydroxy Vitamin D3 Level and Expression of Vitamin D Receptor and Cathelicidin in Pulmonary Tuberculosis. J Clin Immunol 29, 470–478 (2009). https://doi.org/10.1007/s10875-009-9277-9

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Keywords

  • 1,25 Dihydroxy vitamin D3
  • vitamin D receptor
  • cathelicidin
  • tuberculosis