Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.
<h4>Background</h4>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 ep...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0120510 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331079448625152 |
|---|---|
| author | Fabio Bucchieri Antonella Marino Gammazza Alessandro Pitruzzella Alberto Fucarino Felicia Farina Peter Howarth Stephen T Holgate Giovanni Zummo Donna E Davies |
| author_facet | Fabio Bucchieri Antonella Marino Gammazza Alessandro Pitruzzella Alberto Fucarino Felicia Farina Peter Howarth Stephen T Holgate Giovanni Zummo Donna E Davies |
| author_sort | Fabio Bucchieri |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| format | Article |
| id | doaj-art-378bc17dfd8547daaeb46cae1943c8ee |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-378bc17dfd8547daaeb46cae1943c8ee2025-08-20T03:46:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012051010.1371/journal.pone.0120510Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.Fabio BucchieriAntonella Marino GammazzaAlessandro PitruzzellaAlberto FucarinoFelicia FarinaPeter HowarthStephen T HolgateGiovanni ZummoDonna E Davies<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0120510 |
| spellingShingle | Fabio Bucchieri Antonella Marino Gammazza Alessandro Pitruzzella Alberto Fucarino Felicia Farina Peter Howarth Stephen T Holgate Giovanni Zummo Donna E Davies Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors. PLoS ONE |
| title | Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors. |
| title_full | Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors. |
| title_fullStr | Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors. |
| title_full_unstemmed | Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors. |
| title_short | Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors. |
| title_sort | cigarette smoke causes caspase independent apoptosis of bronchial epithelial cells from asthmatic donors |
| url | https://doi.org/10.1371/journal.pone.0120510 |
| work_keys_str_mv | AT fabiobucchieri cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT antonellamarinogammazza cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT alessandropitruzzella cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT albertofucarino cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT feliciafarina cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT peterhowarth cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT stephentholgate cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT giovannizummo cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors AT donnaedavies cigarettesmokecausescaspaseindependentapoptosisofbronchialepithelialcellsfromasthmaticdonors |