Nuclear receptors in inflammation control: repression by GR and beyond.
Nuclear receptors in inflammation control: repression by GR and beyond.
复制标题
DOI：
10.1016/j.mce.2013.04.006
复制
发表时间：
2013-11-05
影响因子：
4.1
通讯作者：
Rogatsky I
中科院分区：
文献类型：
--
作者：
Chinenov Y;Gupte R;Rogatsky I
炎症是生物体对病原体、刺激或损伤的保护性反应。原发性炎症传感器激活一系列信号传导途径，这些信号传导途径最终聚集在一些转录因子上，如AP 1、NFκB和STAT，这些转录因子反过来刺激炎症基因的表达，以最终根除感染并修复损伤。炎症通路的激活和抑制之间的失衡可以为慢性炎症奠定基础，慢性炎症越来越多地被认为是自身免疫性、代谢性、心血管和神经退行性疾病的关键致病成分。核受体（Nuclear Receptors，NR）是一个转录因子大家族，其中许多转录因子以其有效的抗炎作用而闻名。通过小的亲脂性配体激活，NR与广泛的转录因子、辅因子和染色质修饰酶相互作用，组装许多具有不同活性的细胞和组织特异性DNA-蛋白质转录调控复合物。在这里，我们讨论了既定的和新兴的作用和机制，其中NR，特别是糖皮质激素受体（GR）抑制基因编码的细胞因子，趋化因子和其他促炎介质。
Inflammation is a protective response of organisms to pathogens, irritation or injury. Primary inflammatory sensors activate an array of signaling pathways that ultimately converge upon a few transcription factors such as AP1, NFκB and STATs that in turn stimulate expression of inflammatory genes to ultimately eradicate infection and repair the damage. A disturbed balance between activation and inhibition of inflammatory pathways can set the stage for chronic inflammation which is increasingly recognized as a key pathogenic component of autoimmune, metabolic, cardiovascular and neurodegenerative disorders. Nuclear Receptors (NRs) are a large family of transcription factors many of which are known for their potent anti-inflammatory actions. Activated by small lipophilic ligands, NRs interact with a wide range of transcription factors, cofactors and chromatin-modifying enzymes, assembling numerous cell- and tissue-specific DNA-protein transcriptional regulatory complexes with diverse activities. Here we discuss established and emerging roles and mechanisms by which NRs and, in particular, the glucocorticoid receptor (GR) repress genes encoding cytokines, chemokines and other pro-inflammatory mediators.