Gene expression profiles in dendritic cells conditioned by 1α,25-dihydroxyvitamin D3 analog

Matthew D. Griffin, Nianzeng Xing, Rajiv Kumar

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Inhibition of dendritic cell (DC) maturity is an important immunomodulatory effect of 1α,25-dihydroxyvitamin D3 (1α,25(OH) 2D3) and related analogs (D3 analogs). The mechanisms underlying 1α,25(OH)2D3-mediated DC modulation are Vitamin D receptor (VDR)-dependent and likely involve direct or indirect regulation of multiple genes. Gene expression profiles of bone marrow-derived DCs (BMDCs) generated in the absence or presence of a potent D3 analog were analyzed using microarray technology. Results for D3 analog-conditioned DCs were also compared with glucocorticoid-conditioned BMDCs and with BMDCs conditioned with D3 analog and glucocorticoid combined. Of ∼12,000 gene products assayed, 52% were considered to have detectable expression in unconditioned BMDCs. Based on relative expression levels, 5.3% of these expressed genes were "silenced" or "suppressed" in D3 analog-conditioned BMDCs and 2.1% were "augmented". In addition, 1.7% of gene products undetectable in control BMDCs were "induced" by D3 analog. Functional grouping of modulated genes demonstrated important effects of D3 analog on immunoreceptors, on chemokines and chemokine receptors, on growth factors/cytokines and related receptors, and on neuroendocrine hormones and related receptors. Many of these gene products were unaffected or differently regulated by glucocorticoid suggesting specific VDR-mediated regulatory effects. Confirmation of microarray analysis results for two differentially regulated chemokines (MIP-1α and RANTES) was obtained by RT-PCR and ELISA. The methodology provides novel insights into DC gene regulation by 1α,25(OH)2D3 agonists.

Original languageEnglish (US)
Pages (from-to)443-448
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume89-90
DOIs
StatePublished - May 1 2004

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Keywords

  • Antigen presentation
  • Chemokines
  • Dendritic cells
  • Gene chip array
  • Glucocorticoids
  • Vitamin D

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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