Dimerization of glucocorticoid receptors and its role in inflammation and immune responses.

Abstract Glucocorticoids (GCs) plays an irreplaceable role in inflammation and immune responses, fat metabolism and sugar metabolism, it is often used for the treatment of asthma, rheumatoid arthritis and allergic rhinitis clinically, but long-term or high-dose use will produce adverse drug reactions (ADRs). Its biological action is mediated by glucocorticoid receptors (GRs), of which the oligomerization state is closely related to the target gene of which the GRs act. A leading hypothesis is that the beneficial anti-inflammatory effects of GCs occur through the transrepression mechanism mediated by GR monomers, while ADRs may be dependent on the transactivation mechanism mediated by GR dimers. However, in recent years, multiple studies have shown that the transactivation and transrepression functions of the GR dimer also confer anti-inflammatory effects. Furthermore, some studies have shown that some selective glucocorticoid receptor agonists and modulators (SEGRAMs) have good separation characteristics (i.e., preferentially mediate the transrepression of proinflammatory genes or preferentially activate anti-inflammatory target genes). This article reviewed the formation of GR dimers, the role of GR dimers in the inflammation and immune responses, and the progress of SEGRAMs to provide novel ideas for further understanding the anti-inflammatory mechanism of GR and the development of SEGRAMs.