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


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).


CONCLUSIONS
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.
Inui
N
N
Department of Internal Medicine, Second Division, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Murayama
A
A
Sasaki
S
S
Suda
T
T
Chida
K
K
Kato
S
S
Nakamura
H
H
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016516:CD4-CD8 Ratio; D002118:Calcium / Q000378:metabolism; D002128:Calcium Metabolism Disorders / Q000209:etiology / Q000378:metabolism; D053493:Cholestanetriol 26-Monooxygenase; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D017565:Sarcoidosis, Pulmonary / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D015415:Biomarkers; D012333:RNA, Messenger; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D002118:Calcium