Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells
Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells
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DOI：
10.1002/jlb.66.6.909
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发表时间：
1999-12-01
影响因子：
5.5
通讯作者：
Vuk-Pavlovic, S
中科院分区：
文献类型：
--
作者：
Matasic, R;Dietz, AB;Vuk-Pavlovic, S
为了研究皮质类固醇如何影响人树突状细胞（DC）在特定炎症环境中的分化，我们在肿瘤坏死因子α存在的情况下，将未成熟DC与地塞米松孵育（TNF-α）、白细胞介素-1 β（IL-1 β）和前列腺素E-2，地塞米松抑制分化为成熟DC，如抗原呈递分子表达减少所示，共刺激和粘附分子，成熟DC的标志物，IL-12，地塞米松增加了CD 14，CD 36和CD 68的表达，单核细胞/巨噬细胞的特征分子和诱导的CD 14（+）CD 83（-）细胞，一个亚群，与未成熟DC和成熟DC不同。与T和B细胞不同，在DC中地塞米松不诱导凋亡，尽管它抑制活化的核转录因子NF-κ B。地塞米松降低DC刺激同种异体T细胞增殖的能力，与群体中CD 14（+）CD 83（-）细胞的水平成比例。从地塞米松处理的群体中分离的CD 83（+）细胞保留了IL-12的合成和刺激同种异体T细胞增殖的能力。我们的数据表明，尽管存在炎性细胞因子，但药物的主要作用是重新定向细胞亚群的分化。观察到的ID 50值表明，DC分化的抑制可能有助于显着在体内的免疫抑制，通过长期给药的皮质类固醇。
To investigate how corticosteroids affect differentiation of human dendritic cells (DC) in a defined inflammatory environment, we incubated immature DC with dexamethasone in the presence of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and prostaglandin E-2, Dexamethasone inhibited differentiation into mature DC, as indicated by the reduced expression of antigen-presenting molecules, costimulatory and adhesion molecules, a marker of mature DC, and IL-12, Dexamethasone increased expression of CD14, CD36, and CD68, molecules characteristic of monocytes/ macrophages and induced CD14(+)CD83(-) cells, a subset distinct both from immature DC and mature DC, The effects Tc-ere concentration-dependent? with ID50 values between 2 and 30 nM dexamethasone, Unlike T and B cells, in DC dexamethasone induced no apoptosis, although it suppressed activated nuclear transcription factor NF-kappa B. Dexamethasone reduced the ability of DC to stimulate proliferation of allogeneic T cells in proportion to the level of CD14(+)CD83(-) cells in the population. CD83(+) cells, isolated from dexamethasone-treated populations, retained the synthesis of IL-12 and the ability to stimulate proliferation of allogeneic T cells, Our data demonstrate that the dominant effect of the drug was redirecting differentiation of a subset of cells despite the presence of inflammatory cytokines. The observed ID50 values indicate that inhibition of DC differentiation might contribute significantly to in vivo immunosuppression by chronic administration of corticosteroids.