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

Am J Med. 2001 Jun 15;110(9):687-93. doi: 10.1016/s0002-9343(01)00724-0.


Purpose: To demonstrate expression of the 25-hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase) gene in human alveolar macrophages and measure the correlations among the 1 alpha-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 1 alpha-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 1 alpha-hydroxylase was demonstrated in purified human alveolar macrophages. The 1 alpha-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 1 alpha-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 1 alpha-hydroxylase mRNA and the percentage of alveolar lymphocytes (r = 0.82, P <0.05).

Conclusion: There is a correlation between 1 alpha-hydroxylase gene expression in alveolar macrophages with the activity of sarcoidosis and its associated disturbances in calcium metabolism.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-CD8 Ratio
  • Calcium / metabolism
  • Calcium Metabolism Disorders / etiology
  • Calcium Metabolism Disorders / metabolism
  • Cholestanetriol 26-Monooxygenase
  • Female
  • Humans
  • Macrophages, Alveolar / enzymology*
  • Male
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • Sarcoidosis, Pulmonary / complications
  • Sarcoidosis, Pulmonary / enzymology*
  • Sarcoidosis, Pulmonary / pathology
  • Steroid Hydroxylases / biosynthesis*
  • Steroid Hydroxylases / genetics
  • Transcription, Genetic


  • Biomarkers
  • RNA, Messenger
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Calcium