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.

Responses of A549 human lung epithelial cells to cristobalite and α-quartz exposures assessed by toxicoproteomics and gene expression analysis

“…These results were in line with our proteomic and cytotoxicity assay results. In agreement, a recent genomic study (using microarray) on the toxicity of MI reported that the particle perturbed the expression of genes in A549 cells that govern cellular growth and proliferation, cell death, inflammatory response and cell cycle (Sellamuthu et al ., ). More importantly, our gene expression analysis revealed a characteristic difference between CR and MI exposures.…”

“…For this purpose, a panel of 89 genes was selected for gene expression analysis (Supporting information Table S2). Some of these selected genes were known to be affected by silica particles in the literature (Sellamuthu et al, 2011), some were genes upstream and/or downstream of those proteins in the identified pathways based on the proteomic changes in the present study, and some were selected from unrelated pathways. Of the genes selected, 37 were found to exhibit altered expression following particle exposures (Supporting information Table S3).…”

Assessment of genetic toxicity with major inhalable mineral granules in A549 cells

“…To evaluate the harm to cells by inhalable mineral granules which constitute the bulk of the granules, are important factors that should not be ignored. Scientifically objective evaluation of the components of inhalable mineral granules that pose a danger to cells could provide the basis for developing standards to detect and reduce it in the environment (Zhang et al, 2005;Sellamuthu et al, 2011;Maisanaba et al, 2014 …”

Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis

“…Silicosis, an irreversible and incurable disease, is the most consequential adverse health effect associated with silica exposure. To understand the underlying mechanisms of silicosis, global gene expression profiling by employing microarray, or newer sequencing platforms, and bioinformatic analysis of gene expression data were utilized 15 , 16 , 17 . However, there are still some missing gaps in this aspect.…”