Luo Min, Simons S Stoney
Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, National Institutes of Health, Bethesda, MD 20892-1772, USA.
Hum Immunol. 2009 Oct;70(10):785-9. doi: 10.1016/j.humimm.2009.07.029. Epub 2009 Aug 6.
Glucocorticoids are widely used for their anti-inflammatory and immunosuppressive properties. Changing concentrations of transcriptional cofactors or chemicals in transiently transfected tissue culture cells modify several properties of glucocorticoid receptor-regulated gene expression including total activity (A(max)), agonist steroid potency (EC(50)), and the percentage of full agonist activity for antisteroids (percent partial agonist activity). However, no reports exist for endogenous genes in primary human cells. Here we document that reduced concentrations of TIF2, a p160 coactivator, in peripheral blood mononuclear cells modulate these parameters for endogenous genes in a gene-selective manner, thus establishing the physiological relevance of this behavior.
糖皮质激素因其抗炎和免疫抑制特性而被广泛应用。在瞬时转染的组织培养细胞中,转录辅因子或化学物质浓度的变化会改变糖皮质激素受体调节的基因表达的若干特性,包括总活性(A(max))、激动剂类固醇效力(EC(50))以及抗类固醇的完全激动剂活性百分比(部分激动剂活性百分比)。然而,关于原代人细胞中内源性基因的情况尚无相关报道。在此我们证明,外周血单核细胞中p160共激活因子TIF2浓度的降低以基因选择性方式调节内源性基因的这些参数,从而确立了这种行为的生理相关性。