The p38 MAPK is a signaling pathway important for cells to respond to environmental and intracellular stress. Upon activation, the p38 kinase phosphorylates downstream effectors, which control the inflammatory response and coordinate fundamental cellular processes such as proliferation, apoptosis, and differentiation. Dysregulation of this signaling pathway has been linked to inflammatory diseases and cancer. Secretion of glucocorticoids (GCs) is a classical endocrine response to stress. The glucocorticoid receptor (GR) is the primary effector of GCs and plays an important role in the regulation of cell metabolism and immune response by influencing gene expression in response to hormone-dependent activation. Its ligands, the GCs or steroids, in natural or synthetic variation, are used as standard therapy for anti-inflammatory treatment, severe asthma, autoimmune diseases, and several types of cancer. Several years ago, the GR was identified as one of the downstream targets of p38, and, at the same time, it was shown that glucocorticoids could influence p38 signaling. In this review, we discuss the role of the crosstalk between the p38 and GR in the regulation of gene expression in response to steroids and comprehend the importance and potential of this interplay in future clinical applications.
Keywords: MAPK; cancer; crosslink; drug discovery; glucocorticoid receptor; glucocorticoids; inflammation; inhibitor; p38; signaling.