IMMUNOSUPPRESSION BY GLUCOCORTICOIDS - INHIBITION OF NF-KAPPA-B ACTIVITY THROUGH INDUCTION OF I-KAPPA-B SYNTHESIS
IMMUNOSUPPRESSION BY GLUCOCORTICOIDS - INHIBITION OF NF-KAPPA-B ACTIVITY THROUGH INDUCTION OF I-KAPPA-B SYNTHESIS
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DOI：
10.1126/science.270.5234.286
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发表时间：
1995-10-13
期刊：
影响因子：
56.9
通讯作者：
KARIN, M
中科院分区：
文献类型：
--
作者：
AUPHAN, N;DIDONATO, JA;KARIN, M
糖皮质激素是最有效的抗炎和免疫抑制剂之一。它们抑制几乎所有已知的细胞因子和免疫功能所需的几种细胞表面分子的合成，但这种活性的机制尚不清楚。本文表明，糖皮质激素是小鼠和培养细胞中核因子κ B（NF-κ B）活化的有效抑制剂，这种抑制是通过诱导I κ B α抑制蛋白介导的，该抑制蛋白将活化的NF-κ B捕获在无活性的胞质复合物中。由于NF-κ B激活许多免疫调节基因以响应促炎刺激，因此其活性的抑制可以是糖皮质激素抗炎活性的主要组分。
Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function, but the mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-kappa B) activation in mice and cultured cells, This inhibition is mediated by induction of the I kappa B alpha inhibitory protein, which traps activated NF-kappa B in inactive cytoplasmic complexes. Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids.