Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects.
Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects.
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DOI：
10.1186/s12865-021-00413-z
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发表时间：
2021-03-26
期刊：
影响因子：
3
通讯作者：
Chuang CC
中科院分区：
文献类型：
--
作者：
Chang WT;Hong MY;Chen CL;Hwang CY;Tsai CC;Chuang CC
糖皮质激素（Glucocorticoids，GC）是临床感染性和炎症性疾病的重要调节剂。GC受体（GR）是属于核受体家族的转录因子，其调节抗炎过程并释放促炎细胞因子，例如白细胞介素（IL）-6。在IL-6启动子上发现了5个GR结合位点和其他转录因子结合位点，地塞米松（DEX）可抑制脂多糖（LPS）诱导的IL-6产生。在突变的转录因子结合位点中，核因子-κ B（NF-κB）、激活蛋白（AP）-1和特异性蛋白（Sp）1-2位点通过各种反应降低基础和LPS诱导的IL-6启动子活性。第二个GR结合位点（GR 2）被认为在LPS诱导的炎症中的基础和诱导型启动子活性中起着至关重要的作用。我们的结论是，选择性GR 2调节剂可能发挥激动和拮抗作用，并能激活LPS刺激的炎症过程中的关键信号通路。在线版本包含补充材料，可通过10.1186/s12865-021-00413-z获得。
Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1–2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process. The online version contains supplementary material available at 10.1186/s12865-021-00413-z.
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