Correlation between 25-hydroxyvitamin D3 1α-hydroxylase gene expression in alveolar macrophages and the activity of sarcoidosis

Abstract

PURPOSE: To demonstrate expression of the 25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase) gene in human alveolar macrophages and measure the correlations among the 1α-hydroxylase mRNA level, the activity of sarcoidosis, and calcium metabolism. SUBJECTS AND METHODS: We examined 7 patients with sarcoidosis and 6 control patients with other pulmonary disorders who underwent bronchoalveolar lavage. Levels of 1α-hydroxylase mRNA were measured by semiquantitative polymerase chain reaction amplification. We measured serum levels of calcium, ionized calcium, parathyroid hormone, calcitriol (1,25-dihydroxyvitamin D3), and 25-hydroxyvitamin D3 to evaluate calcium metabolism. To estimate the activity of sarcoidosis, we measured the cell count, the CD4/CD8 ratio in bronchoalveolar lavage cells, and the serum angiotensin-converting enzyme (ACE) activity. RESULTS: Expression of 1α-hydroxylase was demonstrated in purified human alveolar macrophages. The 1α-hydroxylase mRNA levels in bronchoalveolar lavage cells were fivefold higher in sarcoidosis patients than in control patients (10.8 ± 3.6 vs. 2.2 ± 1.4, P <0.003). Among all patients studied, there were significant correlations between the 1α-hydroxylase mRNA level in bronchoalveolar lavage samples and the percentage of alveolar lymphocytes ( r = 0.83, P <0.005), the CD4/CD8 ratio ( r = 0.77, P <0.02), serum ACE level ( r = 0.58, P <0.05), serum ionized calcium level ( r = 0.58, P <0.05), and the calcitriol/25-hydroxyvitamin D3 ratio ( r = 0.57, P <0.05). In the sarcoidosis patients, a significant correlation was also observed between 1α-hydroxylase mRNA and the percentage of alveolar lymphocytes ( r = 0.82, P <0.05). CONCLUSION: There is a correlation between 1α-hydroxylase gene expression in alveolar macrophages with the activity of sarcoidosis and its associated disturbances in calcium metabolism.