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Budesonide, Aclidinium and Formoterol in combination limit inflammaging processes in bronchial epithelial cells exposed to cigarette smoke.
- Source :
-
Experimental gerontology [Exp Gerontol] 2019 Apr; Vol. 118, pp. 78-87. Date of Electronic Publication: 2019 Jan 16. - Publication Year :
- 2019
-
Abstract
- Inflammation and cellular senescence (also called inflammaging) are involved in the pathogenesis of premature lung aging, a key driver of chronic obstructive pulmonary disease (COPD). Downregulation of histone deacetylases and FoxO3 expression, activation of the ERK 1/2 pathway and IL-8 increase are hallmarks of lung inflammaging. The effects of Budesonide (BUD), Aclidinium (ACL) and Formoterol (FO) on lung inflammaging are unknown. This study was aimed to assess the effects of BUD, ACL and FO in bronchial epithelial cells exposed to cigarette smoke extract (CSE) by evaluating: a) Expression of TLR4 and survivin and LPS binding by flow cytometry; b) expression of HDAC2, HDAC3, SIRT1 and FoxO3 and activation of the ERK 1/2 pathway by western blot; c) IL-8 mRNA levels and release by Real Time-PCR and ELISA, respectively. Reported results show that CSE increased TLR4 and survivin, LPS binding, ERK 1/2 activation, IL-8 release and mRNA levels but decreased SIRT1, HDAC2, HDAC3 and FoxO3 nuclear expression. Combined therapy with BUD, ACL and FO counteracted the effects of CSE on LPS binding, FoxO3 nuclear expression, ERK 1/2 activation, survivin and IL-8 release and mRNA levels. These findings suggest a new role of combination therapy with BUD, ACL and FO in counteracting inflammaging processes induced by cigarette smoke exposure.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Cells, Cultured
Extracellular Signal-Regulated MAP Kinases physiology
Forkhead Box Protein O3 metabolism
Humans
Lipopolysaccharides metabolism
Sirtuin 1 analysis
Toll-Like Receptor 4 analysis
Bronchi drug effects
Budesonide administration & dosage
Cellular Senescence drug effects
Epithelial Cells drug effects
Formoterol Fumarate administration & dosage
Inflammation prevention & control
Smoke adverse effects
Nicotiana adverse effects
Tropanes administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6815
- Volume :
- 118
- Database :
- MEDLINE
- Journal :
- Experimental gerontology
- Publication Type :
- Academic Journal
- Accession number :
- 30659954
- Full Text :
- https://doi.org/10.1016/j.exger.2019.01.016