Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles

Abstract

Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.

Resistance to Nano-Based Antifungals Is Mediated by Biomolecule Coronas

“…fumigatus and other fungal species . The immune system of healthy individuals, namely the alveolar macrophages and neutrophils, is able to dispose of inhaled conidia ,,, These are the same cells which are known to be activated as the body’s response to exposure with nanoparticles (NPs). − Yet, effective strategies to improve the outcome for patients with invasive mycoses represent an enormous medical challenge.…”

Ensure Healthy Lives and Promote Well-Being for All At All Ages

“…3.5), and it is this needle-like structure that makes asbestos highly invasive and persistent, especially in the lungs. The pathways by which asbestos causes lung diseases are not fully understood, however it is widely reported that asbestos induces inflammation, tissue damage, and DNA and chromosomal damage (Nymark et al 2008;Yanamala et al 2018). Research efforts into the mechanisms for the asbestos induced disease are ongoing, and key breakthroughs in understanding the pathogenesis of diseases associated with this mineral fibre will allow for important progress in the prevention and treatment of asbestosrelated diseases.…”

Mesothelioma Interactome with 367 Novel Protein-Protein Interactions

“…A recent study has reported the genes that were differentially expressed in lungs of mice exposed to crocidolite and erionite fibers compared to a control group (54). Crocidolite and erionite are asbestos or asbestos-like particles that are capable of inducing lung cancer and/or mesothelioma in humans and animal models (54).…”

“…A recent study has reported the genes that were differentially expressed in lungs of mice exposed to crocidolite and erionite fibers compared to a control group (54). Crocidolite and erionite are asbestos or asbestos-like particles that are capable of inducing lung cancer and/or mesothelioma in humans and animal models (54). Out of the 1,710 genes differentially expressed on crocidolite exposure, 160 genes were part of the MPM interactome (p-value of overlap =3.63E-05), and 6 out of 78 genes differentially expressed on erionite exposure occured in the MPM interactome ( Figure 4 and Data File 3).…”