Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

Abstract

A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure.

Keywords::

• Crystalline silica
• pulmonary toxicity
• gene expression profile
• mechanisms

Acknowledgements

The authors thank Bean Chen, Amy Cumpston, Jared Cumpston, David Frazer, Howard Leonard, and Walter McKinney (NIOSH, Morgantown, WV) for assistance with inhalation exposure of rats to crystalline silica. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of NIOSH. The microarray data have been deposited in the Gene Expression Omnibus Database, http://www.ncbi.nlm.nih.gov/geo (accession number GSE30216).

Declaration of interest

The authors report no declaration of interest.