Fibrogenic effects of crocidolite, amosite, and chrysotile asbestos fibers on lung fibroblasts

초록

Asbestos causes fibrotic lung diseases such as asbestosis and lung scarring, but the molecular mechanisms underlying the effects of specific types of asbestos fibers are not fully understood. The objective of this study was to investigate the fibrogenic activity of commonly used asbestos types crocidolite (serpentine) and amosite and chrysotile (amphiboles) which differ in general toxicity. IMR-90 lung fibroblasts were exposed to various concentrations of crocidolite, amosite, and chrysotile and analyzed for viability, adhesion, cell damage, functional activity, and expression of genes associated with fibrosis, cell stress, and toxicity responses. Exposure of fibroblasts to the three asbestos fibers for 48 h did not affect cellular functions such as filamentous actin distribution and mitochondrial activity. PCR microarray profiling of the expression of 84 genes central to fibrogenesis revealed that chrysotile significantly upregulated the transcription of genes encoding pro-fibrotic cytokines and downregulated genes related to the transforming growth factor-beta superfamily, whereas the effects of crocidolite and amosite on pro-fibrotic gene expression were much weaker. There was no significant difference in the expression of oxidative stress- and toxic response-related genes among the three asbestos types. These results provide new evidence that chrysotile has a stronger pro-fibrotic potential than amosite and crocidolite. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

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