FIGURE 9.

Schematic summary of how PPARγ, GR-α, and HDAC2 affect transcription of NF-κB target genes in COPD. Top panel, cigarette smoke-induced inflammatory signaling, which leads to degradation and post-translational inhibitory modifications of PPARγ, along with HDAC2 and GR-α, results in histone acetylation and chromatin unwinding. This allows NF-κB and its associated coactivators to bind to target promoters and stimulate transcription by RNA polymerase II (RNA Pol II). Bottom panel, activation of PPARγ up-regulates HDAC2 and GR-α expression in addition to expression of PPARγ itself. This results in removal of histone acetyl groups and condensation of chromatin structure, blocking NF-κB and RNA polymerase II binding. NF-κB activity is further reduced by binding to PPARγ and GR-α and, through GR-α, to HDAC2, as well as by PPARγ competition for essential coactivators.