Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthm

A Nadeem

Alberto Fucarino

Alessandro Pitruzzella

AM Merendino

Antonella Marino Gammazza

B Halliwell

C Bazzini

C Xiao

DE Davies

Donna E. Davies

DR Bergren

DS Postma

EJ Swindle

F Bucchieri

Fabio Bucchieri

Felicia Farina

Ferenc Gallyas

Giovanni Zummo

GR Hellermann

H Carp

H Sugiura

I Gonzalez-Suarez

IA Fedorov

II Olatunji-Bello

JB Sedgwick

K Gangl

K Iwanaga

K Kovacs

KK Stone

L Galluzzi

LG Wood

LJ Smith

M Aubier

M Contoli

M Curvall

M Siedlinski

M van der Toorn

N Gumral

P Kirkham

PAB Wark

Peter Howarth

RJ Freishtat

S Pierrou

SA Comhair

SJ van Wijk

SM Puddicombe

SP Faux

ST Holgate

Stephen T. Holgate

SW Yu

T To

TL Hackett

X Liu

PLoS ONE

PubMed

BackgroundEpidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke.ObjectivesSince primary bronchial epithelial cells (PBECs) from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death.MethodsPBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were assessed by fluorescence-activated cell sorting, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF).ResultsExposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH), but not ascorbic acid (AA), protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective.ConclusionOur results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma

Stephen T Holgate

Donna E Davies

Directory of Open Access Journals

Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.

Bucchieri, Fabio

Marino Gammazza, Antonella

Pitruzzella, Alessandro

Fucarino, Alberto

Farina, Felicia

Howarth, Peter

Holgate, Stephen T

Zummo, Giovanni

Davies, Donna E

Southampton (e-Prints Soton)

Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors

Background: Epidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke. Objectives: Since primary bronchial epithelial cells (PBECs) from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death. Methods: PBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were assessed by fluorescence-activated cell sorting, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF). Results: Exposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH), but not ascorbic acid (AA), protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective. Conclusion: Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma

BUCCHIERI, Fabio

MARINO GAMMAZZA, Antonella

PITRUZZELLA, Alessandro

FUCARINO, Alberto Giuseppe

FARINA, Felicia

Howarth, P.

Holgate, S.

ZUMMO, Giovanni

Davies, D.

Archivio istituzionale della ricerca - Università di Palermo

Crossref

Epidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke. Since primary bronchial epithelial cells (PBECs) from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death. PBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were assessed by FACS, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF). Exposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH), but not ascorbic acid (AA), protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective. Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma

Holgate, Stephen T.

Cappello, Francesco

Davies, Donna E.

Firenze University Press: E-Journals

IJAE 
Vo l .  119,  n .  1  (Supp lem ent) :  24 ,  2014
© 2014 Firenze University Press 
ht tp://www.fupress .com/ijae
ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY
Cigarette smoke causes caspase-independent 
apoptosis of bronchial epithelial cells from asthmatic 
donors
Fabio Bucchieri1,2,3, Antonella Marino Gammazza2,3 Alessandro Pitruzzella2,3, Alberto Fucarino2, 
Peter Howarth1,4, Stephen T. Holgate1,4, Francesco Cappello2,3, Felicia Farina2, Giovanni Zummo2, 
Donna E. Davies1,4
1 Academic Unit of Clinical and Experimental Sciences, University of Southampton School of Medicine, 
University Hospital Southampton, Southampton, UK
2 Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy
3 Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
4 Southampton NIHR Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, University of 
Southampton School of Medicine, University Hospital Southampton, Southampton, UK
Epidemiologic studies have demonstrated important links between air pollution 
and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor 
both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environ-
ment, the bronchial epithelium is a key structure that is exposed to cigarette smoke. 
Since primary bronchial epithelial cells (PBECs) from asthmatic donors are more sus-
ceptible to oxidant-induced apoptosis, we hypothesized that they would be suscepti-
ble to cigarette smoke-induced cell death. PBECs from normal and asthmatic donors 
were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were 
assessed by FACS, and protective effects of antioxidants evaluated. The mechanism of 
cell death was evaluated using caspase inhibitors and immunofluorescent staining for 
apoptosis-inducing factor (AIF). Exposure of PBEC cultures to CSE resulted in a dose-
dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibit-
ed significantly more apoptosis than cells from non-asthmatic controls. Reduced glu-
tathione (GSH), but not ascorbic acid (AA), protected against CSE-induced apoptosis. 
To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were 
tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear trans-
location of AIF from the mitochondria. GSH reduced the number of nuclear-AIF posi-
tive cells whereas AA was ineffective. Our results show that PBECs from asthmatic 
donors are more susceptible to CSE-induced apoptosis. This response involves AIF, 
which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial 
susceptibility to CSE may contribute to the impact of environmental tobacco smoke in 
asthma. 
Keywords
Bronchial epithelium, cigarette smoke extract, apoptosis-inducing factor, asthma.


https://iris.unipa.it/retrieve/handle/10447/148525/229056/pone.0120510%281%29.pdf

Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors

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Directory of Open Access Journals

Southampton (e-Prints Soton)

Archivio istituzionale della ricerca - Università di Palermo

Crossref

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