Role of inflammation in the malignant transformation of pleural mesothelial cells induced by multi-walled carbon nanotubes

• Published in: Nanotoxicology 2020-08, Vol.14 (7), p.947-967
• Main Authors: Huang, Xiaopei, Tian, Yijun, Shi, Wenjing, Chen, Jikuai, Yan, Lang, Ren, Lijun, Zhang, Xiaofang, Zhu, Jiangbo
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cell Movement - drug effects; Cell Movement - immunology; Cell proliferation; Cell Proliferation - drug effects; co-culture system; Coculture Techniques; Cytokines; Cytokines - metabolism; Dosage; Dose-Response Relationship, Drug; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - pathology; Exposure; Gene Knockdown Techniques; Genetic transformation; High aspect ratio; Humans; IL-1β; Inflammation; Interleukin 6; Interleukin 8; Interleukin-1beta - metabolism; Leukocyte migration; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - pathology; malignant pleural mesothelioma; Mesothelioma; Mesothelioma - immunology; Mesothelioma - metabolism; Mesothelioma - pathology; Mesothelioma, Malignant; Multi wall carbon nanotubes; Multi-walled carbon nanotubes; Nanofibers; Nanomaterials; Nanotechnology; Nanotubes; Nanotubes, Carbon - toxicity; NF-κB protein; NF-κB/IL-6/STAT3 pathway; Occupational safety; Stat3 protein; THP-1 Cells; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Transformations; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 1743-5390; 1743-5404
• DOI: 10.1080/17435390.2020.1777477

Multi-walled carbon nanotubes (MWCNTs) are one of the most widely used types of novel nano-fiber materials. The aim of this study was to establish an experimental system based on actual exposure dosage and environments and explore the roles and mechanisms of inflammation in the malignant transformation of pleural mesothelial cells induced by MWCNTs after low doses and long-term exposure. Here, we established an in vitro system by co-culturing macrophages and mesothelial cells and exposing these cells to high aspect ratio MWCNTs (0.1 μg/mL) for three months. Results indicated that IL-1β, secreted by macrophages stimulated by MWCNTs, may significantly enhance the release of inflammatory cytokines, such as IL-8, TNF-α, and IL-6, from mesothelial cells. Results obtained from proliferation, migration, invasion, colony formation, and chromosomal aberration studies indicated that MWCNTs may promote malignant transformation of mesothelial cells after long-term and low-dose exposure via inflammation. Furthermore, the obtained results demonstrated that the NF-κB/IL-6/STAT3 pathway was active in the malignant transformation of Met 5A cells, induced by MWCNTs, and played an important role in the process. In conclusion, our results showed that the NF-κB (p65)/IL-6/STAT3 molecular pathway, which was mediated by inflammation, played an important role in the malignant transformation of pleural mesothelial cells induced by MWCNTs. These findings also provide novel ideas and references for the treatment of mesothelioma and offers options for the occupational safety of nanomaterial practitioners.