English: Figure 2. Theophylline directly activates histone deacetylases (HDACs) which deacetylate core histones that have been acetylated by the histone acetyltransferase (HAT) activity of co-activators, such as CREB-binding protein (CBP). This results in suppression of inflammatory genes and proteins, such as granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-8 (IL-8) that have been switched on by proinflammatory transcription factors, such as nuclear factor-κB (NF-κB). Corticosteroids also activate HDACs, but through a different mechanism resulting in the recruitment of HDACs to the activated transcriptional complex via activation of the glucocorticoid receptors (GR) which function as a molecular bridge. This predicts that theophylline and corticosteroids may have a synergistic effect in repressing inflammatory gene expression.