Abstract
Dendritic cell (DC) maturation plays a central role in regulating immunity. We show that glucocorticoid and 1α,25(OH)2D3 agonists modulate DCs via distinct and additive signaling pathways. Phenotypic and functional indices were examined in DCs treated with dexamethasone (DEX) and/or a 1α,25(OH)2D3 analog (D3 analog). DEX potently attenuated pro-inflammatory cytokines and chemokines but had modest, reversible effects on T-cell stimulatory capacity. D3 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-1α. Both DEX and D3 analog were associated with reduced expression of the NF-κB proteins c-Rel and Rel B but not Rel A. Combined DEX and D3 analog treatment of DCs resulted in significant additive inhibition of pro-inflammatory cytokines, T-cell stimulation, chemokines, chemokine receptors, and NF-κB 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.
Original language | English (US) |
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Pages (from-to) | 645-652 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 297 |
Issue number | 3 |
DOIs | |
State | Published - 2002 |
Keywords
- Antigen presentation
- Chemokines
- Dendritic cells
- Glucocorticoid
- Immune responses
- Interleukin 12
- Nuclear factor κB
- Steroid hormones
- T lymphocytes
- Vitamin D
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology