Glucocorticoid receptor signaling: crosstalk with inflammation

OBJECTIVE: Glucocorticoids (GCs) represent a vital group of steroid hormones naturally occurring in humans, with the ability to be synthesized artificially as well. They are essential in facilitating the normal physiological functions of mammals. Within typical physiological ranges, GCs chiefly contribute to the regulation of metabolism and the maintenance of homeostasis. When given in elevated pharmacological doses, GCs offer anti-inflammatory and immunosuppressive advantages, making them key treatments for various inflammatory conditions and immune-related disorders. By improving our understanding of glucocorticoid receptor (GR) biology and the molecular processes that underpin GC actions, we seek to clarify the influence of GCs on the immune system and their role in facilitating anti-inflammatory responses, ultimately offering insights for creating novel therapeutic approaches to enhance the beneficial effects of GCs. METHODS: This review conducts a thorough analysis of GR, elaborating on its structure, function, and involvement in inflammation by investigating the molecular processes that might enhance the efficacy of GCs in addressing both inflammatory and infectious disorders. RESULTS: The interaction between GCs and GR is crucial for regulating the expression of various inflammatory genes. This regulation occurs primarily through two mechanisms: transrepression and transactivation. CONCLUSIONS: Both intracellular and extracellular signals modulate GR activity at various stages, underscoring the importance of understanding GR structure, activation processes, and the interplay of pathways to create innovative therapies that target GR signaling, either independently or in combination with other treatments.