Occupational and environmental exposures to airborne
asbestos and
silica are associated with the development of lung
fibrosis in the forms of
asbestosis and
silicosis, respectively. However, both diseases display distinct pathologic presentations, likely associated with differences in gene expression induced by different
mineral structures, composition and bio-persistent properties. We hypothesized that effects of
mineral exposure in the airway epithelium may dictate deviating molecular events that may explain the different pathologies of
asbestosis versus
silicosis. Using robust gene expression-profiling in conjunction with in-depth pathway analysis, we assessed early (24 h) alterations in gene expression associated with
crocidolite asbestos or
cristobalite silica exposures in primary human bronchial epithelial cells (NHBEs). Observations were confirmed in an immortalized line (BEAS-2B) by QRT-PCR and
protein assays. Utilization of overall gene expression, unsupervised hierarchical cluster analysis and integrated pathway analysis revealed gene alterations that were common to both minerals or unique to either
mineral. Our findings reveal 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. These findings illustrate the use of gene-profiling as a means to determine early molecular events that may dictate
pathological processes induced by exogenous cellular insults. In addition, it is a useful approach for predicting the pathogenicity of potentially harmful materials.