Cigarette smoke compounds induce cellular redox imbalance, activate NF-κB, and increase TNF-α/CRP secretion: a possible pathway in the pathogenesis of COPD.

Cigarette smoke has always been considered as a risk factor for chronic obstructive pulmonary diseases (COPD). In this study, we have examined the effect of ten individual cigarette smoke compounds (nicotine, benzo[a]pyrene, naphthalene, formaldehyde, ammonia, acrylic acid, toluene, benzene, m-xylene, and hexamine) on glutathione S transferase (GST) activity, an important Phase II metabolic enzyme and their possible role in inflammatory pathophysiology leading to COPD. Lower Glutathione (GSH) levels and GST activity and higher CRP, TNF-α, and IL-6 levels were observed in COPD patients compared to age and gender-matched controls. Using human recombinant GST and plasma as well as erythrocytes collected from normal subjects this study demonstrates that out of the ten compounds, nicotine (5 mg mL-1), benzo[a]pyrene (10 ng mL-1), naphthalene (250 μg mL-1), and formaldehyde (5 pg mL-1) caused a significant decrease in recombinant, plasma, and erythrocyte GST activity. Further cell culture studies show that exposure to nicotine, benzo[a]pyrene, naphthalene, and formaldehyde caused a significant decrease in GSH levels and GST activity and its protein expression and an increase in intracellular ROS production in THP-1 monocytes. Interestingly, treatment with benzo[a]pyrene and naphthalene significantly up regulated the phosphorylation of the p65 subunit of NF-κB and increased the secretion of TNF-α and CRP compared to control. This study suggests the potential role of benzo[a]pyrene and naphthalene in the activation of the inflammatory signaling pathway leading to cigarette smoke-induced COPD.