Abstract
Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), airway obstruction, wheezing, and leads to airway remodeling if these symptoms persist. Airway remodeling is characterized by goblet hyperplasia, airway smooth muscle hypertrophy and hyperplasia, subepithelial fibrosis and denudation of the epithelium. Due to weakened protection of the airway epithelium, the body is more susceptible to infections and exacerbation of asthma symptoms.|Airway epithelial cells are damaged and shed during airway remodeling, a characteristic of chronic asthma. During airway remodeling inflammatory cells including eosinophils and neutrophils penetrate the epithelium leading destruction of the tissue. Eosinophils, primary inflammatory cells, release TGF-ßl, a potent mediator of epithelial damage. Expression of TGF-ßl is higher in asthmatics. TGF-ßl can induce apoptosis of airway epithelial cells, however, the underlying mechanism of apoptosis is not well defined. A new member of the TNF superfamily, TRAIL, is predominantly involved in apoptosis. Various studies in hepatoma cells have linked the pathways of TRAIL and TGF-ßl.|Given this information, we hypothesized that TGF-ßl induced apoptosis of airway epithelial cells occurs through the actions of TRAIL. We investigated the role of TGF-ßl in the proliferation and apoptosis of human airway epithelial cells. Also we examined the effect of TGF-ßl on the mRNA transcript and protein expression of TRAIL. To investigate whether TGF-ßl induced apoptosis via TRAIL, we performed a study in which the receptor of TRAIL was blocked to observe whether caspase-dependent apoptosis still occurs. TGF-ßl induced the release of TRAIL by airway epithelial cells. Upon TGF-ßl treatment, proliferation decreased while apoptosis increased. The mRNA transcript and protein expression was increased upon treatment with TGF-ßl. The expression of activated caspase-3 was increased with TGF-ßl treatment as well as the increased expression of Bax. However, there was a decreased expression of Bcl-2. When TRAIL-R2 was blocked, there is no apoptosis induced by TGF-ßl through the actions of caspases.|These data suggest that TGF-ßl induced apoptosis occurs through the actions of TRAIL and its receptors and may have potential in therapy for treating asthma.