Paul M Peeters
Maastricht University, The Netherlands
Title: Gene expression profiling of the response of lung epithelial cells to particles and fibers: Can we predict phenotypic outcomes?
Biography
Biography: Paul M Peeters
Abstract
Asbestosis and silicosis display distinct pathological presentations, likely associated with differences in gene expression induced by mineral structures, composition and bio-persistent properties. The effects of different minerals exposed in the airway epithelium may dictate deviating molecular events explaining the different pathologies. Microarray analysis in conjunction with in-depth pathway analysis revealed early alterations in gene expression associated with crocidolite asbestos or cristobalite silica exposures in primary human bronchial epithelial cells. Overall gene expression, unsupervised hierarchical cluster analysis and integrated pathway analysis demonstrated gene alterations that were common to both minerals or unique to either mineral. Our findings revealed that both minerals had potent effects on genes governing cell adhesion/migration, inflammation, and cellular stress, key features of fibrosis. Asbestos exposure was most specifically associated with aberrant cell proliferation and carcinogenesis, whereas silica exposure was highly associated with additional inflammatory responses, as well as pattern recognition, and fibrogenesis. Toxicological testing of particulates by surveying viability and/or metabolic activity is useful but insufficient to predict their pathogenicity. Therefore assessment of the degree and magnitude of these responses by microarrays in vitro could be predictive in determining the pathogenicity of potentially harmful molecules.