Rhinovirus-16 induced release of IP-10 and IL-8 is augmented by Th2 cytokines in a pediatric bronchial epithelial cell model.
BACKGROUND
In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation.


METHODS
Primary bronchial epithelial cell cultures from pediatric subjects were treated with Th2 cytokines for 24 h before infection with RV16. Release of IL-8, IP-10 and GM-CSF was measured by ELISA. Infection was quantified using RTqPCR and TCID50. Phosphatidyl inositol 3-kinase (PI3K) and P38 mitogen activated protein kinase (MAPK) inhibitors and dexamethasone were used to investigate differences in signaling pathways.


RESULTS
The presence of Th2 cytokines did not affect RV replication or viral titre, yet there was a synergistic increase in IP-10 release from virally infected cells in the presence of Th2 cytokines. Release of IL-8 and GM-CSF was also augmented. IP-10 release was blocked by a PI3K inhibitor and IL-8 by dexamethasone.


CONCLUSIONS
Th2 cytokines increase release of inflammatory cytokines in the presence of rhinovirus infection. This increase is independent of effects of virus replication. Inhibition of the PI3K pathway inhibits IP-10 expression.
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom.
Julie A
JA
Cakebread
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom.
Hans Michael
HM
Haitchi
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom.
Yunhe
Y
Xu
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
Stephen T
ST
Holgate
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
Graham
G
Roberts
Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.
Donna E
DE
Davies
D000293:Adolescent; D001980:Bronchi; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D012229:Rhinovirus / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D054357:Chemokine CXCL10; D016207:Cytokines; D016209:Interleukin-8