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

Vitamin D-3, which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations between low serum vitamin D-3 levels and increased risk of tuberculosis have been reported. Plasma 1,25 dihydroxy vitamin D-3 levels (1,25(OH)(2) D-3) 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 D-3. VDR and CYP27B1 (-1077 A/T) gene polymorphisms were studied using PCR-based methods. 1,25(OH)(2) D-3 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) D-3 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 D-3-treated cultures compared to unstimulated and M. tuberculosis-stimulated culture in both patients (p < 0.001) and NHS (p < 0.05). The present study suggests that PTB patients may have increased 1,25(OH)(2) D-3 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) D-3 might lead to increased expression of cathelicidin which could enhance the immunity against tuberculosis.