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 Citations (Scopus)

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 2004

Fingerprint

Calcitriol
Transcriptome
Gene expression
Dendritic Cells
Bone
Genes
Bone Marrow
Glucocorticoids
Calcitriol Receptors
Microarrays
Chemokines
Chemokine CCL5
Chemokine Receptors
Cytokine Receptors
Microarray Analysis
Intercellular Signaling Peptides and Proteins
Modulation
Hormones
Cytokines
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Gene expression profiles in dendritic cells conditioned by 1α,25-dihydroxyvitamin D3 analog. / Griffin, Matthew D.; Xing, Nianzeng; Kumar, Rajiv.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 89-90, 05.2004, p. 443-448.

Research output: Contribution to journalArticle

@article{8b8c45df66e44d7db34a3ca0fac667b7,
title = "Gene expression profiles in dendritic cells conditioned by 1α,25-dihydroxyvitamin D3 analog",
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.",
keywords = "Antigen presentation, Chemokines, Dendritic cells, Gene chip array, Glucocorticoids, Vitamin D",
author = "Griffin, {Matthew D.} and Nianzeng Xing and Rajiv Kumar",
year = "2004",
month = "5",
doi = "10.1016/j.jsbmb.2004.03.039",
language = "English (US)",
volume = "89-90",
pages = "443--448",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Gene expression profiles in dendritic cells conditioned by 1α,25-dihydroxyvitamin D3 analog

AU - Griffin, Matthew D.

AU - Xing, Nianzeng

AU - Kumar, Rajiv

PY - 2004/5

Y1 - 2004/5

N2 - 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.

AB - 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.

KW - Antigen presentation

KW - Chemokines

KW - Dendritic cells

KW - Gene chip array

KW - Glucocorticoids

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=3042554099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042554099&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2004.03.039

DO - 10.1016/j.jsbmb.2004.03.039

M3 - Article

VL - 89-90

SP - 443

EP - 448

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

ER -