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Cell Stress and Chaperones

, Volume 18, Issue 6, pp 733–743 | Cite as

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

  • Elisabetta PaceEmail author
  • Maria Ferraro
  • Serena Di Vincenzo
  • Chiara Cipollina
  • Stefania Gerbino
  • Diego Cigna
  • Valentina Caputo
  • Rossella Balsamo
  • Luigi Lanata
  • Mark Gjomarkaj
Original Paper

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.

Keywords

Cigarette smoke Airway epithelial cells Reactive oxygen species 

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

Notes

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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Copyright information

© Cell Stress Society International 2013

Authors and Affiliations

  • Elisabetta Pace
    • 1
    • 6
    Email author
  • Maria Ferraro
    • 1
  • Serena Di Vincenzo
    • 1
    • 2
  • Chiara Cipollina
    • 1
    • 3
  • Stefania Gerbino
    • 1
  • Diego Cigna
    • 1
  • Valentina Caputo
    • 4
  • Rossella Balsamo
    • 5
  • Luigi Lanata
    • 5
  • Mark Gjomarkaj
    • 1
  1. 1.Institute of Biomedicine and Molecular ImmunologyNational Research Council—PalermoPalermoItaly
  2. 2.Scienze e Biotecnologie Mediche e Sperimentali-Pneumologia Sperimentale e ClinicaUniversità degli Studi—PalermoPalermoItaly
  3. 3.Fondazione Ri.MedPalermoItaly
  4. 4.Department of DermatologyUniversity of PalermoPalermoItaly
  5. 5.Medical AffairDompé SPA MilanMilanItaly
  6. 6.Istituto di Biomedicina e Immunologia MolecolareConsiglio Nazionale delle RicerchePalermoItaly

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