Distinctive dendritic cell modulation by vitamin D3 and glucocorticoid pathways

被引:97
作者
Xing, NZ
Maldonado, ML
Bachman, LA
McKean, DJ
Kumar, R
Griffin, MD
机构
[1] Mayo Clin & Mayo Fdn, Transplant Ctr, Div Nephrol, Dept Internal Med, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
[4] Mayo Clin & Mayo Fdn, Mayo Proteom Res Ctr, Rochester, MN 55905 USA
关键词
dendritic cells; antigen presentation; steroid hormones; vitamin D; glucocorticoid; chemokines; nuclear factor kappa B; interleukin; 12; T lymphocytes; immune responses;
D O I
10.1016/S0006-291X(02)02262-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (133 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. (C) 2002 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:645 / 652
页数:8
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