Desmet Sofie J, De Bosscher Karolien
J Clin Invest. 2017 Apr 3;127(4):1136-1145. doi: 10.1172/JCI88886. Epub 2017 Mar 20.
Glucocorticoids (GCs; referred to clinically as corticosteroids) are steroid hormones with potent anti-inflammatory and immune modulatory profiles. Depending on the context, these hormones can also mediate pro-inflammatory activities, thereby serving as primers of the immune system. Their target receptor, the GC receptor (GR), is a multi-tasking transcription factor, changing its role and function depending on cellular and organismal needs. To get a clearer idea of how to improve the safety profile of GCs, recent studies have investigated the complex mechanisms underlying GR functions. One of the key findings includes both pro- and anti-inflammatory roles of GR, and a future challenge will be to understand how such paradoxical findings can be reconciled and how GR ultimately shifts the balance to a net anti-inflammatory profile. As such, there is consensus that GR deserves a second life as a drug target, with either refined classic GCs or a novel generation of nonsteroidal GR-targeting molecules, to meet the increasing clinical needs of today to treat inflammation and cancer.
糖皮质激素（GCs；临床上称为皮质类固醇）是具有强大抗炎和免疫调节特性的类固醇激素。根据具体情况，这些激素也可介导促炎活性，从而充当免疫系统的启动因子。它们的靶受体，即糖皮质激素受体（GR），是一种多功能转录因子，会根据细胞和机体需求改变其作用和功能。为了更清楚地了解如何改善糖皮质激素的安全性，最近的研究调查了GR功能背后的复杂机制。其中一项关键发现包括GR的促炎和抗炎作用，未来的一个挑战将是理解如何调和这些矛盾的发现，以及GR最终如何将平衡转向净抗炎状态。因此，人们一致认为，GR作为药物靶点值得重获新生，无论是通过改良经典糖皮质激素还是新一代非甾体类GR靶向分子，以满足当今治疗炎症和癌症不断增长的临床需求。
