Apoptosis of viral-infected airway epithelial cells limit viral production and is altered by corticosteroid exposure.
BACKGROUND
Effects of respiratory viral infection on airway epithelium include airway hyper-responsiveness and inflammation. Both features may contribute to the development of asthma. Excessive damage and loss of epithelial cells are characteristic in asthma and may result from viral infection.


OBJECTIVE
To investigate apoptosis in Adenoviral-infected Guinea pigs and determine the role of death receptor and ligand expression in the airway epithelial response to limit viral infection.


METHODS
Animal models included both an Acute and a Chronic Adeno-infection with ovalbumin-induced airway inflammation with/without corticosteroid treatment. Isolated airway epithelial cells were cultured to study viral production after infection under similar conditions. Immunohistochemistry, western blots and viral DNA detection were used to assess apoptosis, death receptor and TRAIL expression and viral release.


RESULTS
In vivo and in vitro Adeno-infection demonstrated different apoptotic and death receptors (DR) 4 and 5 expression in response to corticosteroid exposure. In the Acute Adeno-infection model, apoptosis and DR4/5 expression was coordinated and were time-dependent. However, in vitro Acute viral infection in the presence of corticosteroids demonstrated delayed apoptosis and prolonged viral particle production. This reduction in apoptosis in Adeno-infected epithelial cells by corticosteroids exposure induced a prolonged virus production via both DR4 and TRAIL protein suppression. In the Chronic model where animals were ovalbumin-sensitized/challenged and were treated with corticosteroids, apoptosis was reduced relative to adenovirus-infected or corticosteroid alone.


CONCLUSIONS
Our data suggests that apoptosis of infected cells limits viral production and may be mediated by DR4/5 and TRAIL expression. In the Acute model of Adeno-infection, corticosteroid exposure may prolong viral particle production by altering this apoptotic response of the infected cells. This results from decreased DR4 and TRAIL expression. In the Chronic model treated with corticosteroids, a similar decreased apoptosis was observed. This data suggests that DR and TRAIL modulation by corticosteroids may be important in viral infection of airway epithelium. The prolonged virus release in the setting of corticosteroids may result from reduced apoptosis and suppressed DR4/TRAIL expression by the infected cells.
Singhera
Gurpreet K
GK
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research/ Critical Care Group, St, Paul's Hospital, University of British Columbia, Vancouver, British Columbia, V6Z-1Y6, Canada. Gsinghera@mrl.ubc.ca
Chan
Tiffany S
TS
Cheng
Jenny Y
JY
Vitalis
Timothy Z
TZ
Hamann
Kimm J
KJ
Dorscheid
Delbert R
DR
D000208:Acute Disease; D000256:Adenoviridae / Q000254:growth & development*; D000257:Adenoviridae Infections / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D006168:Guinea Pigs; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000150:complications; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014132:Trachea / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D014771:Virion / Q000502:physiology
D000893:Anti-Inflammatory Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; D019819:Budesonide; D010047:Ovalbumin