Role of budesonide, formoterol fumarate and aclidinium bromide in the inflammaging of airway epithelial cells

Abstract

Rationale: Chronic inflammation and cellular senescence (also called inflammaging) are deeply involved in the pathogenesis of premature lung aging, an important contributing factor in driving chronic obstructive pulmonary disease (COPD). SIRT1, activating FoxO3 transcription factor protects against lung inflammaging. FoxO3, deacetylated by SIRT1, within the nucleus binds to the survivin promoter thus blocking the survivin gene transcription However, phosphorylation of FoxO3 promotes FoxO3 nuclear export and protein degradation. Aims: The aims of the study were to assess the effects of budesonide (BUD), aclidinium (ACL) and formoterol (FO) on inflammaging processes of bronchial epithelial cells exposed to cigarette smoke. Lipopolysaccharide (LPS) binding and survivin expression were assessed by flow-cytometry, ERK 1/2 pathway activation and nuclear expression of SIRT1, HDAC3, FoxO3 were assessed by western-blot analysis. Real time PCR was applied to assess IL-8 and telomerase mRNA expression. Results. Here, it was demonstrated that, in bronchial epithelial cells, Cigarette smoke extract (CSE) increased LPS binding, ERK 1/2 pathway activation, IL-8 mRNA and survivin expression but decreased SIRT1, HDAC3, FoxO3 nuclear and telomerase mRNA expression. A combination of BUD, ACL and FO is able to counteract the effects of CSE on the LPS binding, FoxO3 nuclear expression, ERK 1/2 pathway activation, survivin and IL-8 mRNA expression. Conclusions: These findings suggest a new effect of combination with BUD, ACL and FO in counteracting inflammaging processes induced by cigarette smoke exposure.