Distinctive dendritic cell modulation by vitamin D(3) and glucocorticoid pathways.
Distinctive dendritic cell modulation by vitamin D(3) and glucocorticoid pathways.
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DOI：
10.1016/s0006-291x(02)02262-3
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发表时间：
2002-09
影响因子：
3.1
通讯作者：
N. Xing;Monica L L Maldonado-Monica-L-L-Maldonado-15074187;L. Bachman;D. McKean;R. Kumar;M. Griffin
中科院分区：
文献类型：
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作者：
N. Xing;Monica L L Maldonado-Monica-L-L-Maldonado-15074187;L. Bachman;D. McKean;R. Kumar;M. Griffin
树突状细胞（DC）的成熟在免疫调节中起着重要作用。我们发现糖皮质激素和1α，25（OH）2D 3激动剂通过不同的和叠加的信号通路调节DC。检测地塞米松（DEX）和/或1α，25（OH）2D 3类似物（D3类似物）处理的DC的表型和功能指标。DEX有效地减弱促炎细胞因子和趋化因子，但对T细胞刺激能力具有适度的可逆作用。D3类似物在体外和体内均能显著抑制T细胞的刺激作用，与DEX不同，D3类似物能增加趋化因子MCP-1和MIP-1α的表达。DEX和D3类似物均与NF-κB蛋白c-Rel和Rel B的表达减少有关，但与Rel A无关。DCs的DEX和D3类似物组合处理导致促炎细胞因子、T细胞刺激、趋化因子、趋化因子受体和NF-κB组分的显著叠加抑制。RANTES、CCR 5、CCR 7和Rel B的相加抑制作用最为显著。两种激素途径对DC的联合作用具有独特的免疫调节潜力。
Dendritic cell (DC) maturation plays a central role in regulating immunity. We show that glucocorticoid and 1α,25(OH)2D3agonists 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)2D3analog (D3analog). DEX potently attenuated pro-inflammatory cytokines and chemokines but had modest, reversible effects on T-cell stimulatory capacity. D3analog 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 D3analog were associated with reduced expression of the NF-κB proteins c-Rel and Rel B but not Rel A. Combined DEX and D3analog 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.