Source: International Congress 2014 – Novel epigenetic regulators for targeting via nanomedicine
Disease area: Airway diseases

Abstract

Cigarette smoke exposure, increasing oxidative stress, may negatively affects corticosteroid responses in COPD patients and in smokers with asthma. The effects of formoterol on the molecular mechanisms of corticosteroid resistance in the human bronchial epithelial cells stimulated with cigarette smoke extract (CSE)are unknown.This study explored whether the formoterol alone and in combination with the fluticasone propionate, in a bronchial epithelial cell line, counteracted some molecular mechanisms associated to corticosteroid resistance. Hystone Deacetylase (HDAC)-3 activity and expression, nuclear translocation of Glucorticoid Receptor (GR) and NF-KB, in bronchial epithelial cells which were stimulated with CSE and/or formoterol and fluticasone propionate were explored. HDAC-3 activity was measured by a commercial kit, nuclear translocation of HDAC-3, GR and NF-KB were assessed on cytoplasmic and nuclear protein extracts by western-blot analysis. CSE decreased activity as well as the nuclear expression of HDAC-3, decreased the expression of GR in the cytoplasm and in the nucleus, increased the nuclear expression of NF-KB. Formoterol alone and in combination with fluticasone propionate in CSE stimulated bronchial epithelial cells reverts these phenomena increasing the expression of HDAC-3, the nuclear translocation of Glucorticoid Receptor and decreasing nuclear translocation of NF-KB.In conclusion, the present study provides evidences that formoterol may contribute to revert some processes induced by smoke and may improve fluticasone propionate responses.Funded by Consiglio Nazionale delle Ricerche.

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Citations should be made in the following way:
M. Ferraro, M. Gjomarkaj, S. Di Vincenzo, R. Balsamo, E. Pace (Palermo, Italy). Effects of formoterol on the molecular mechanisms of corticosteroid resistance in models with high oxidative stress. Eur Respir J 2014; 44: Suppl. 58, 194

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