Glucocorticoid suppression of activated inflammatory genes

Inflammatory genes are activated by inflammatory stimuli, such as interleukin-1b (IL-1b) or tumor necrosis factor-a (TNF-a), resulting in activation of IKK2 (inhibitor of I-kB kinase-2), which activates the transcription factor nuclear factor kB (NF-kB). A dimer of p50 and p65 NF-kB proteins translocates to the nucleus and binds to specific kB recognition sites and also to coactivators, such as CREB-binding protein (CBP) or p300/CBP-activating factor (pCAF), which have intrinsic histone acetyltransferase (HAT) activity. This results in acetylation of core histone H4, resulting in increased expression of genes encoding multiple inflammatory proteins. Glucocorticoid receptors (GR) after activation by glucocorticoids translocate to the nucleus and bind to coactivators to inhibit HAT activity directly and recruiting histone deacetylase-2 (HDAC2), which reverses histone acetylation leading in suppression of these activated inflammatory genes.