Center for Inflammation Research, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Front Immunol. 2019 Jul 4;10:1545. doi: 10.3389/fimmu.2019.01545. eCollection 2019.
Glucocorticoids (GCs) are steroid hormones widely used for the treatment of inflammation, autoimmune diseases, and cancer. To exert their broad physiological and therapeutic effects, GCs bind to the GC receptor (GR) which belongs to the nuclear receptor superfamily of transcription factors. Despite their success, GCs are hindered by the occurrence of side effects and glucocorticoid resistance (GCR). Increased knowledge on GC and GR biology together with a better understanding of the molecular mechanisms underlying the GC side effects and GCR are necessary for improved GC therapy development. We here provide a general overview on the current insights in GC biology with a focus on GC synthesis, regulation and physiology, role in inflammation inhibition, and on GR function and plasticity. Furthermore, novel and selective therapeutic strategies are proposed based on recently recognized distinct molecular mechanisms of the GR. We will explain the SEDIGRAM concept, which was launched based on our research results.
糖皮质激素（GCs）是一种广泛用于治疗炎症、自身免疫性疾病和癌症的甾体激素。为了发挥其广泛的生理和治疗作用，GCs 与糖皮质激素受体（GR）结合，GR 属于核受体超家族转录因子。尽管 GC 治疗取得了成功，但 GC 仍存在副作用和糖皮质激素抵抗（GCR）的问题。因此，需要进一步深入了解 GC 和 GR 的生物学特性，以及 GC 副作用和 GCR 的分子机制，以开发出更好的 GC 治疗方法。本文主要概述了 GC 生物学的最新研究进展，包括 GC 的合成、调控和生理学作用、在炎症抑制中的作用，以及 GR 的功能和可塑性，并基于 GR 的不同分子机制提出了新的、选择性的治疗策略。此外，本文还介绍了基于我们的研究成果而提出的 SEDIGRAM 概念。
