Abstract
Within the airway, the epithelium forms the first structural cell defense against common environmental insults such as respiratory syncytial virus (RSV) and particulate matter. These stimuli have been shown to be associated with exacerbations of the disease, which contribute to the financial burden of asthma.
Objective: Characterize the intrinsic phenotype of asthmatic and non-asthmatic airway epithelium and determine their inflammatory responses to RSV and particulate matter (EHC-93) exposure.
Methods: Air-liquid interface cultures (ALICs) were generated from asthmatic and non-asthmatic airway epithelial cells. Airway tissue and ALICs were analyzed by immuno for Cytokeratin-5, E-cadherin, Ki67, Muc5AC, and apoptosis. ALI cultures were exposed to RSV (4×106 PFU/ml) or EHC-93 (100μg/ml) for 24, 48, and 96 h and supernatants analyzed for pro-inflammatory cytokines using ELISA.
Results: The airway epithelium of asthmatics in vivo and in ALIC demonstrated a less differentiated epithelium characterized by elevated numbers of cells expressing basal cell markers CK-5 and Ki67 and less adherens junction protein E-cadherin (p<0.01), though trans-epithelial resistance was not different compared to non-asthmatic ALICs. In response to RSV infection and PM10 exposure, asthmatic ALICs released greater levels of IL-6, IL-8 and GM-CSF compared to non-asthmatic ALICs (P<0.05). This enhanced cytokine expression was not due to enhanced p38 or NF-kB expression.
Conclusion: This parallel ex vivo and in vitro study demonstrates that the asthmatic epithelium displays an intrinsic alteration in phenotype and responds with an enhanced inflammatory profile to RSV and particulate matter.
- © 2011 ERS