Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF‐κB activation and proinflammatory cytokine release in alveolar epithelial cells

Oxidative stress is implicated in lung inflammation due to its effect on proinflammatory gene transcription. Changes in gene transcription depend on chromatin remodeling and the relative activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Alterations in the nuclear histone acetylation:deacetylation balance may result in uncontrolled transcription of specific proinflammatory genes. We studied the effect of hydrogen peroxide (H 2 O 2 ) and cigarette smoke condensate (CSC) on histone acetylation:deacetylation in human alveolar epithelial cells (A549). H 2 O 2 and CSC significantly increased acetylation of histone H4 proteins and were associated with decreased HDAC activity and HDAC2 levels in A549 cells. Also, the decreased HDAC2 activity was due to protein modification by aldehydes and nitric oxide products. Pretreatment of A549 cells with N ‐acetyl‐L‐cysteine attenuated the oxidant‐mediated reduction in HDAC activity. Treatment of A549 cells with CSC did not cause nuclear factor‐κB (NF‐κB) activation or expression and release of either interleukin (IL)‐8 or IL‐6. However, H 2 O 2 , tumor necrosis factor‐α (TNF‐α), and IL‐1β significantly increased NF‐κB activation and expression of IL‐8 compared with control cells. Interestingly, CSC dose dependently inhibited TNF‐α‐ and IL‐ 1β‐mediated NF‐κB activation and IL‐8 expression. Thus, H 2 O 2 and CSC enhance acetylation of histone proteins and decrease histone deacetylase activity but differentially regulate proinflammatory cytokine release in alveolar epithelial cells.