Anti-inflammatory effects of formoterol and fluticasone propionate in bronchial epithelial cells

Abstract

The addition of long-acting b2-agonists (LABAs) to corticosteroids improves asthma control. Cigarette smoke exposure increasing oxidative stress, increases airway inflammation and may negatively affect corticosteroid responses. The anti-inflammatory effects of formoterol (FO) and fluticasone propionate (FP) in human bronchial epithelial cells (16HBE) exposed to cigarette smoke extracts (CSE) are unknown. Aims: This study was aimed to explore whether FO, alone or combined with FP, counteracts some CSE-mediated effects in 16HBE including: 1) the nuclear translocation of Glucorticoid Receptor (GR); 2) the nuclear expression of NF-KB; 3) the expression of the NF-KB related cytochines IL-8 and TNFa. Methods: 16HBE were stimulated with CSE and/or FO and FP. Nuclear translocation of GR and NF-KB were assessed by western-blot analysis. IL-8 and TNFa exspression were valuated by Real-time PCR. Results: CSE decreased the expression of GR and increased the expression of nuclear NF-KB. FO, alone and combined with FP, was able to revert these phenomena in CSE stimulated 16HBE cells increasing the nuclear translocation of GR and decreasing the nuclear translocation of NF-KB. FO combined with FP reduced the expression of IL-8 and TNFa and this phenomenon was maintained in the presence of cigarette smoke. Conclusion: s: The present study provides compelling evidences that FO may contribute to reverse some processes induced by oxidative stress and is able to increase the anti-inflammatory effects of FP.