Efeitos anti-inflamatórios do salbutamol e epímero da resolvina D1 (AT-RVD1) em células epiteliais brônquicas humanas estimuladas com extrato de fumaça de cigarro

Abstract

Smoking is one of the most serious health concerns causing high rates of morbidity and mortality and several diseases such as chronic obstructive pulmonary disease (COPD). The activation of airway epithelial cells by cigarette smoke and consequent oxidative stress induces the production of several pro-inflammatory mediators that orchestrate and influence the innate and adaptive immune responses. Here, we evaluated the effects of salbutamol (10-5 -10-7M), AT-RvD1 (10-7 -10-12M) and the association of both on human bronchial epithelial cells (BEAS-2B) stimulated with cigarette smoke extract (CSE; 1%; 1 cigarette) for 24 h in vitro. Salbutamol (10-5 and 10-6M) or AT-RvD1 (10-7 -10-11M), reduced the IL-1β production induced by CSE in a dose-response manner. Using the combination of a range of pharmacologically effective concentrations from each compound, except the combination of non-effective doses from both, the association AT-RvD1 (10-11M) and salbutamol (10-7M) potentiated the reduction of IL-1β production when compared to cells only treated with salbutamol at 10-7 M alone. AT-RvD1 (10-11M), but not salbutamol (10-7M), and the association of both decreased the IL-8 production and increased the IL-10 production without alter the reactive oxygen species production when compared to CSE group. These anti-inflammatory effects could be associated with the down regulation of activation of NF-κB, but not STAT3. AT-RvD1, salbutamol and the association of both reduced the ICAM-1 expression. As such, AT-RvD1 in association with salbutamol could be a potential alternative treatment to airway mucosal inflammation caused by cigarette smoking such as in COPD patients.