Functional block for 1α,25-dihydroxyvitamin D3-mediated gene regulation in human B lymphocytes

John W. Morgan, G. Satyanarayana Reddy, Milan R. Uskokovic, Brian K. May, John L. Omdahl, Abby L. Maizel, Surendra Sharma

Research output: Contribution to journalArticlepeer-review

Abstract

Elements necessary for the steroid hormone 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) to induce a biological response include the presence of specific intracellular receptors (vitamin D3 receptors (VDR)) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes. These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1α,25- (OH)2D3-responsive cells of the T and monocytic lineages. Although resting tonsillar B cells did not express VDR mRNA, activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1α,25- (OH)2D3. As indicators of hormone-mediated gene regulation we analyzed modulation of CD23, a common B cell/monocyte surface antigen, and 24- hydroxylase. 1α,25-(OH)2D3 inhibited CD23 expression in U937 cells, yet failed to modulate CD23 expression in B cells. Furthermore, 1α,25-(OH)2D3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells, yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells. These findings suggest that although human B lymphocytes can express VDR mRNA and protein, they exhibit a functional block for vitamin D-dependent gene regulation.

Original languageEnglish (US)
Pages (from-to)13437-13443
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number18
StatePublished - May 6 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Functional block for 1α,25-dihydroxyvitamin D3-mediated gene regulation in human B lymphocytes'. Together they form a unique fingerprint.

Cite this