Molecular Interaction between the Glucocorticoid Receptor and MAPK Signaling Pathway: A novel link in Modulating the Anti-inflammatory Role of Glucocorticoids.

ABSTRACT

Glucocorticoids (GCs) have a broad spectrum of life-sustaining functions and play an important role in health and diseases. At pharmacologic doses, GCs are potent immunosuppressive and anti-inflammatory agents. Inflammation and its related diseases present a huge ever increasing burden on the health and disease management. A plausible link of inflammation with aging, cardiovascular diseases and cancer makes matter even worst and calls for a better understanding to resolve the mechanisms associated with the cause and cure of inflammation. Understanding the physiological and molecular interlinks is an utmost importance in designing novel therapeutic strategies in combating inflammation. Advancement in research related to the mitogen-activated protein kinase (MAPK) signaling pathway and its regulation on inflammation has open up new and promising avenues in targeting inflammation as well as understanding the anti-inflammatory property of GCs. Molecular interaction between the ligand-activated glucocorticoid receptor (GR) and the MAPK signaling at different junctions inhibit the latter and thus may account for the anti-inflammatory role of GCs. Therapeutic application of GCs in combination with the recently added class of GR modulators having greater transrepresssion over transactivation (dissociative property) might overcome the clinical side effects associated with GCs.