白细胞介素-6 启动子上的突变糖皮质激素受体结合元件调节地塞米松的作用。

Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects.

机构信息

Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, 701, Taiwan.

Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

BMC Immunol. 2021 Mar 26;22(1):24. doi: 10.1186/s12865-021-00413-z.

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

背景

糖皮质激素（GCs）作为临床感染和炎症性疾病中必不可少的调节剂得到了广泛应用。糖皮质激素受体（GR）是核受体家族的转录因子，可调节抗炎过程并释放促炎细胞因子，如白细胞介素（IL）-6。

结果

在 IL-6 启动子上鉴定出 5 个假定的 GR 结合位点和其他转录因子结合位点，地塞米松（DEX）可降低脂多糖（LPS）诱导的 IL-6 产生。在突变转录因子结合位点中，核因子-κB（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了基础和 LPS 诱导的 IL-6 启动子活性。第二个 GR 结合位点（GR2）在 LPS 诱导的炎症中基础和诱导启动子活性中均发挥关键作用。