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Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

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Cell Stress and Chaperones Aims and scope

Abstract

Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10−4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclear-related factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10−8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin V-positive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSE-mediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

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Abbreviations

CSE:

Cigarette smoke extracts

CARB:

Carbocysteine

FP:

Fluticasone propionate

ROS:

Reactive oxygen species

GSH:

Glutathione

HO-1:

Heme oxygenase-1

Nrf2:

Nuclear-related factor 2

HDAC-2:

Histone deacetylase 2

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Acknowledgments

This work was mainly supported by the Italian National Research Council and by Dompè, Italy. Elisabetta Pace declares that she has had access to and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Institute of Biomedicine and Molecular Immunology, National Research Council—Palermo, Palermo, Italy

    Elisabetta Pace, Maria Ferraro, Serena Di Vincenzo, Chiara Cipollina, Stefania Gerbino, Diego Cigna & Mark Gjomarkaj

  2. Scienze e Biotecnologie Mediche e Sperimentali-Pneumologia Sperimentale e Clinica, Università degli Studi—Palermo, Palermo, Italy

    Serena Di Vincenzo

  3. Fondazione Ri.Med, Palermo, Italy

    Chiara Cipollina

  4. Department of Dermatology, University of Palermo, Palermo, Italy

    Valentina Caputo

  5. Medical Affair, Dompé SPA Milan, Milan, Italy

    Rossella Balsamo & Luigi Lanata

  6. Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Via Ugo La Malfa, 153-90146, Palermo, Italy

    Elisabetta Pace

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  1. Elisabetta Pace
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  2. Maria Ferraro
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Correspondence to Elisabetta Pace.

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Pace, E., Ferraro, M., Di Vincenzo, S. et al. Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells. Cell Stress and Chaperones 18, 733–743 (2013). https://doi.org/10.1007/s12192-013-0424-0

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  • DOI: https://doi.org/10.1007/s12192-013-0424-0

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