Oxidants and proinflammatory cytokines activate transcription factors, such as NF-κB, by recruitment of transcriptional coactivator molecules CBP/p300, which possess intrinsic histone acetylase (HAT) activity, resulting in histone acetylation and DNA unwinding, allowing DNA polymerases access to the DNA leading to proinflammatory gene expression. Direct interaction between coactivators (such as HAT), histone deacetylase, and the glucocorticoid receptor (GR) may result in repression of expression of proinflammatory genes. Histone deacetylase type II (HDAC2) forms a bridge with HAT and RelA/p65 to inhibit gene transcription. However, when the HDAC2 (by post-translational modification/disruption) is inhibited by cigarette smoke/oxidants and/or the NF-κB subunit RelA/p65 is acetylated, steroids may not be able to recruit HDAC2 into the transrepressor complex to inhibit proinflammatory gene expression. Dietary polyphenols, such as curcumin and resveratrol inhibit NF-κB activation, CBP-HAT activity, and restore glucocorticoid efficacy by upregulating HDAC2 and sirutin activity, culminating in inhibition of proinflammatory gene expression.