Abstract
Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain.
Highlights
Inflammation and GlucocorticoidsInflammation is described as a response to infection or injury
It has been greatly demonstrated that chronic inflammation is associated with several pathologies, such as obesity [7], cardiovascular diseases [8], rheumatoid arthritis [9], inflammatory bowel disease [10, 11], asthma [12, 13], diabetes [14, 15], neurodegenerative diseases [16], and cancer [17]
Box A pretreatment blocked the stress-induced increase in microglial IL-1β, IKBα, and NLRP3 mRNA expression in response to a bacterial challenge [67]. These results suggest that high-mobility group box-1 protein (HMGB-1) participates in stress-inducing NLRP3 priming, adding another mechanism by which GCs could have pro-inflammatory effects in the brain [67, 69]
Summary
Inflammation and GlucocorticoidsInflammation is described as a response to infection or injury. We will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoid potentiation of pro-inflammatory gene regulation. GR dimerizes and binds to DNA at palindromic GRE sites, activating the promoter as a transcription factor (transactivation), altering gene expression of various proteins.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call