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This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/L617    most recent 00129.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Phokela, S. S. Articles by Alcorn, J. L. Search for Related Content PubMed PubMed Citation Articles by Phokela, S. S. Articles by Alcorn, J. L.

Regulation of human pulmonary surfactant protein gene expression by 1,25-dihydroxyvitamin D₃

¹Department of Pediatrics, Division of Neonatal-Perinatal Medicine, The University of Texas Health Science Center at Houston; and ²Department of Endocrine Disorders, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas

Submitted 6 April 2004 ; accepted in final form 3 June 2005

1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃] has been reported to stimulate lung maturity, alveolar type II cell differentiation, and pulmonary surfactant synthesis in rat lung. We hypothesized that 1,25(OH)₂D₃ stimulates expression of surfactant protein-A (SP-A), SP-B, and SP-C in human fetal lung and type II cells. We found that immunoreactive vitamin D receptor was detectable in fetal lung tissue and type II cells only when incubated with 1,25(OH)₂D₃. 1,25(OH)₂D₃ significantly decreased SP-A mRNA in human fetal lung tissue but did not significantly decrease SP-A protein in the tissue. In type II cells, 1,25(OH)₂D₃ alone had no significant effect on SP-A mRNA or protein levels but reduced SP-A mRNA and protein in a dose-dependent manner when the cells were incubated with cAMP. SP-A mRNA levels in NCI-H441 cells, a nonciliated bronchiolar epithelial (Clara) cell line, were decreased in a dose-dependent manner in the absence or presence of cAMP. 1,25(OH)₂D₃ had no significant effect on SP-B mRNA levels in lung tissue but increased SP-B mRNA and protein levels in type II cells incubated in the absence or presence of cAMP. Expression of SP-C mRNA was unaffected by 1,25(OH)₂D₃ in lung tissue incubated ± cAMP. These results suggest that regulation of surfactant protein gene expression in human lung and type II cells by 1,25(OH)₂D₃ is not coordinated; 1,25(OH)₂D₃ decreases SP-A mRNA and protein levels in both fetal lung tissue and type II cells, increases SP-B mRNA and protein levels only in type II cells, and has no effect on SP-C mRNA levels.

alveolar type II cell; steroid hormone