Figure 4.

Corticosteroids suppression of activated inflammatory genes. Inflammatory genes are activated by inflammatory stimuli, such as IL-1β or TNF-α, resulting in activation of IKK2 (inhibitor of I-κB kinase-2), which activates the transcription factor NF-κB. A dimer of p50 and p65 NF-κB proteins translocates to the nucleus and binds to specific κB recognition sites and also to coactivators, such as CBP or pCAF, which have intrinsic HAT activity. This results in acetylation of core histone H4, resulting in increased expression of genes encoding multiple inflammatory proteins. GR after activation by corticosteroids translocate to the nucleus and bind to coactivators to inhibit HAT activity directly and recruiting HDAC2, which reverses histone acetylation leading in suppression of these activated inflammatory genes.