Effects of Beclomethasone dipropionate and Formoterol in reducing oxidative stress induced by cigarette smoke extracts and IL-17

Rationale: Oxidative stress is involved in airway inflammatory diseases. Inhaled-corticosteroids reduce airway inflammation and the combination with long-acting β2 agonists enhances this effect. Objective: to investigate whether Cigarette smoke extracts (CSE) and Interleukin-17A (IL-17A) activate airway epithelial cells to release markers of oxidative/nitrosative stress and to investigate the effect of beclomethasone dipropionate (BDP) and formoterol. Methods: Human bronchial epithelial cells (16HBE) were stimulated with different concentrations of CSE (from 0 to 10%) to evaluate the expression of IL-17 receptor (IL-17R). 16HBE were also stimulated with CSE (2.5%) with and withouth rhIL-17A (50 ng/ml) to evaluate the production of Reactive oxygen species (Ros), and Nitrotyrosine levels. The effects of BDP (10-8M) and Formoterol (10-8M), alone and in combination, were evaluated. Results: CSE increased the expression of IL-17R in 16HBE in a dose dependent manner with a maximum effect at 2.5% concentration (p<0.001). Both CSE and rhIL-17A separately increased the production of Ros and Nitrotyrosine (p<0.05) and their combination synergistically further increased the production of these markers (p<0.001). BDP alone was able to completely restore the baseline values in terms of IL-17R expression (p<0.001) and its combination with Formoterol was superior in reducing the Ros and Nitrotyrosine production (p<0.001). Conclusions: Cigarette smoke and IL-17A increase the production of oxidative/nitrosative markers in human bronchial epithelial cells, this effect being reduced by BDP either alone or combined with Formoterol.