Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action
Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action
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DOI：
10.1016/s0006-2952(02)01147-4
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发表时间：
2002-09-01
影响因子：
5.8
通讯作者：
Sasson, R
中科院分区：
文献类型：
--
作者：
Amsterdam, A;Tajima, K;Sasson, R
糖皮质激素在减轻炎症反应中起主要作用。这些类固醇激素能够诱导造血系统细胞的凋亡，例如参与炎症反应的单核细胞、巨噬细胞和T淋巴细胞。相反，最近发现，在腺细胞如乳腺上皮细胞、肝细胞、卵巢滤泡细胞和成纤维细胞中，糖皮质激素保护细胞免受细胞因子、cAMP、肿瘤抑制因子和死亡基因引起的凋亡信号的影响。糖皮质激素的抗凋亡作用是通过以细胞特异性方式调节几种存活基因如Bcl-2、Bcl-x（L）和NF κ B来发挥的。此外，在糖皮质激素刺激后，相同基因产物的上调或下调可以以细胞依赖性方式发生。这一现象可能是由于复合调控串扰之间的多个核辅激活因子或辅阻遏物，介导的基因的转录调控，通过它们与糖皮质激素受体的相互作用。这些观察结果表明，糖皮质激素的抗炎作用是由两种互补的机制发挥的：一方面，它们诱导引起炎症的细胞死亡，另一方面，它们通过阻止凋亡信号来保护发炎组织的驻留细胞。此外，糖皮质激素的补充作用为这些激素的治疗潜力提供了新的见解。(C)2002年爱思唯尔科技有限公司All rights reserved.
Glucocorticoids play a major role in attenuation of the inflammatory response. These steroid hormones are able to induce apoptosis in cells of the hematopoietic system such as monocytes, macrophages, and T lymphocytes that are involved in the inflammation reaction. In contrast, it was discovered recently that in glandular cells such as the mammary gland epithelia, hepatocytes, ovarian follicular cells, and in fibroblasts glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumor suppressors, and death genes. The anti-apoptotic effect of glucocorticoids is exerted by modulation of several survival genes such as Bcl-2, Bcl-x(L), and NFkB, in a cell-specific manner. Moreover, upregulation or downregulation of the same gene product can occur in a cell-dependent manner following stimulation by glucocorticoids. This phenomenon is probably due to composite regulatory cross-talk among multiple nuclear coactivators or corepressors, which mediate the transcription regulation of the genes, by their interaction with the glucocorticoid receptor. These observations suggest that the antiinflammatory action of glucocorticoids is exerted by two complementary mechanisms: on one hand, they induce death of the cells that provoke the inflammation, and on the other hand they protect the resident cells of the inflamed tissue by arresting apoptotic signals. Moreover, the complementary action of glucocorticoids provides a new insight to the therapeutic potential of these hormones. (C) 2002 Elsevier Science Inc. All rights reserved.