Distinctive dendritic cell modulation by vitamin D(3) and glucocorticoid pathways

Dendritic cell (DC) maturation plays a central role in regulating immunity. We show that glucocorticoid and 1alpha,25(OH)(2)D(3) agonists modulate DCs via distinct and additive signaling pathways. Phenotypic and functional indices were examined in DCs treated with dexamethasone (DEX) and/or a 1alpha...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-09, Vol.297 (3), p.645-652
Main Authors: Xing, Nianzeng, L Maldonado, Monica L, Bachman, Lori A, McKean, David J, Kumar, Rajiv, Griffin, Matthew D
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Chemokine CCL2 - genetics
Chemokine CCL3
Chemokine CCL4
Chemokine CCL5 - genetics
Cholecalciferol - analogs & derivatives
Cholecalciferol - pharmacology
Culture Media, Conditioned
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dexamethasone - pharmacology
Gene Expression Regulation - drug effects
Gene Expression Regulation - immunology
Glucocorticoids - pharmacology
Macrophage Inflammatory Proteins - genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Antigen, T-Cell - genetics
Receptors, CCR1
Receptors, CCR2
Receptors, Chemokine - genetics
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dendritic cell (DC) maturation plays a central role in regulating immunity. We show that glucocorticoid and 1alpha,25(OH)(2)D(3) agonists modulate DCs via distinct and additive signaling pathways. Phenotypic and functional indices were examined in DCs treated with dexamethasone (DEX) and/or a 1alpha,25(OH)(2)D(3) analog (D(3) analog). DEX potently attenuated pro-inflammatory cytokines and chemokines but had modest, reversible effects on T-cell stimulatory capacity. D(3) analog produced significantly greater inhibition of T-cell stimulation in vitro and in vivo and, unlike DEX, increased expression of the chemokines MCP-1 and MIP-1alpha. Both DEX and D(3) analog were associated with reduced expression of the NF-kappaB proteins c-Rel and Rel B but not Rel A. Combined DEX and D(3) analog treatment of DCs resulted in significant additive inhibition of pro-inflammatory cytokines, T-cell stimulation, chemokines, chemokine receptors, and NF-kappaB components. Additive inhibition was most striking for RANTES, CCR5, CCR7, and Rel B. The combined effects of the two hormonal pathways on DCs have unique immunomodulatory potential.
ISSN:0006-291X