N-acetyl Cysteine Reverts the Proinflammatory State Induced by Cigarette Smoke Extract in Lung Calu-3 Cells

SOTOMAYOR, VERÓNICA; SANTA-COLOMA, TOMÁS A.; SOTOMAYOR, VERÓNICA; SANTA-COLOMA, TOMÁS A.; VALDIVIESO, ÁNGEL G.; CLAUZURE, MARIÁNGELES; VALDIVIESO, ÁNGEL G.; CLAUZURE, MARIÁNGELES; DUGOUR, ANDREA V.; FIGUEROA, JUAN M.; DUGOUR, ANDREA V.; FIGUEROA, JUAN M.

Redox Biology

Redox Biology

Año: 2018 p. 294 - 302

2213-2317

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are lethal pulmonary diseases. Cigaretteconsumption is the main cause for development of COPD, while CF is produced by mutations in the CFTR gene.Although these diseases have a different etiology, both share a CFTR activity impairment and proinflammatorystate even under sterile conditions. The aim of this work was to study the extent of the protective effect of theantioxidant N-acetylcysteine (NAC) over the proinflammatory state (IL-6 and IL-8), oxidative stress (reactive oxygenspecies, ROS), and CFTR levels, caused by Cigarette Smoke Extract (CSE) in Calu-3 airway epithelial cells.CSE treatment (100μg/ml during 24h) decreased CFTR mRNA expression and activity, and increased the releaseof IL-6 and IL-8. The effect on these cytokines was inhibited by N-acetyl cysteine (NAC, 5mM) or the NF-kBinhibitor, IKK-2 (10μM). CSE treatment also increased cellular and mitochondrial ROS levels. The cellular ROSlevels were normalized to control values by NAC treatment, although significant effects on mitochondrial ROSlevels were observed only at short times (5´) and effects on CFTR levels were not observed. In addition, CSE reducedthe mitochondrial NADH-cytochrome c oxidoreductase (mCx I-III) activity, an effect that was not revertedby NAC. The reduced CFTR expression and the mitochondrial damage induced by CSE could not be normalizedby NAC treatment, evidencing the need for a more specific reagent. In conclusion, CSE causes a sterile proinflammatorystate and mitochondrial damage in Calu-3 cells that was partially recovered by NAC treatment.