Deacetylases and NFKB in Redox Regulation of Cigarette Smoke induced Lung Inflammation: Implications in Pathogenesis of COPD

Cigarette smoke-mediated oxidative stress activates the NF-κB pathway leading to acetylation of chromatin on pro-inflammatory genes thus increasing the accessibility of transcription factors leading to increased pro-inflammatory gene expression. Deacetylation results in DNA rewinding around histone proteins, decreasing gene transcription. CBP/p300 function as intrinsic histone acetyltransferases (HATs). Activated corticosteroid receptors recruit HDAC2 into the transcriptome complex promoting histone deacetylation, chromatin condensation and expulsion of DNA polymerases, shutting off gene expression. Cigarette smoke/oxidants inhibit HDAC2 activity (by post-translational modifications) as well as activating NF-κB, facilitating histone acetylation by the transcriptome complex even in the presence of activated glucocorticoid receptor. Theophylline, a methyl xanthine, inhibits pro-inflammatory gene expression via restoring transrepressive pathways through the activation of HDAC2. GC: Glucocorticoid; Ac: Acetylation; 4-HNE: 4-hydroxy-2-nonenol; NO2: Nitric oxide; P: Phosphate; CBP: CREB (cAMP response element binding protein)-binding protein.

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Deacetylases and NF-κB in Redox Regulation of Cigarette Smoke induced Lung Inflammation: Implications in Pathogenesis of COPD. () Saravanan Rajendrasozhan, et al. Antioxid Redox Signal. ;10(4):799-811. Figure: F3. All organisms Drosophila melanogaster Homo sapiens

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