title: Interleukin-9 and -13 inhibit spontaneous and corticosteroid induced apoptosis of normal airway epithelial cells.
abstract: The airway epithelium is the target of physical and allergic insults. The resulting inflammatory signals from Th2 cytokines including interleukin (IL)-9 and IL-13 have pleiotropic activities and have been implicated in airway remodeling in asthmatics. The objective of this study was to determine the role of IL-9 and IL-13 in the regulation of normal airway epithelial cell death and epithelial repair. In a cell culture model, a normal human airway epithelial cell line and primary airway epithelial cells were treated with IL-9 or IL-13 alone and in combination. Apoptosis was determined by multiple techniques, including enrichment of nucleosomes released into the cytoplasm, mitochondrial membrane polarity perturbation, cytosolic cytochrome c released and the detection of cleaved p85-poly(ADP-ribose)polymerase (PARP). Proliferation was quantified by BrdU incorporation. IL-9 and IL-13 treatment, alone and in combination, resulted in a significant reduction in spontaneous airway epithelial cell apoptosis when compared to controls. The cytoprotective effect of IL-9 was associated with up-regulation of the antiapoptotic molecule Bcl-2. IL-13 also demonstrated coordinate pro-proliferative activity .Dexamethasone induces apoptosis in airway epithelial cells. Coincubation with IL-9 or IL-13 was protective against this corticosteroid-induced apoptosis by up-regulation of Bcl-2. These data demonstrate that IL-9 and IL-13 may be critical to normal cellular homeostasis in the setting of airway epithelial injury. A dysregulated response to these cytokines may contribute to airway remodeling in asthma.
authors.affiliation: Providence Healthcare Heart, Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Gurpreet K
authors.initials: GK
authors.lastname: Singhera
authors.forename: Ruth
authors.initials: R
authors.lastname: MacRedmond
authors.forename: Delbert R
authors.initials: DR
authors.lastname: Dorscheid
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology*; D006487:Hemostasis; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D016906:Interleukin-9 / Q000494:pharmacology*; D020011:Protective Agents; D012137:Respiratory System / Q000166:cytology*
chemical_list: D000305:Adrenal Cortex Hormones; D018793:Interleukin-13; D016906:Interleukin-9; D020011:Protective Agents