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.

多壁碳纳米管（MWCNT）是新型纳米纤维材料中使用最广泛的类型之一。这项研究的目的是建立一个基于实际暴露剂量和环境的实验系统，并探讨炎症在低剂量和长期暴露后由MWCNTs诱导的胸膜间皮细胞恶性转化中的作用和机制。在这里，我们建立了一个体外通过共培养巨噬细胞和间皮细胞并将这些细胞暴露于高长径比MWCNT（0.1μg/ mL）中三个月来构建系统。结果表明，由MWCNTs刺激的巨噬细胞分泌的IL-1β可能显着增强炎症性细胞因子（如IL-8，TNF-α和IL-6）从间皮细胞的释放。通过增殖，迁移，侵袭，集落形成和染色体畸变研究获得的结果表明，通过长期和低剂量暴露后，MWCNTs可能促进间皮细胞的恶性转化。炎。此外，获得的结果表明，NF-κB/ IL-6 / STAT3途径在MWCNTs诱导的Met 5A细胞的恶性转化中具有活性，并在该过程中起重要作用。总之，我们的结果表明，由炎症介导的NF-κB（p65）/ IL-6 / STAT3分子途径在MWCNTs诱导的胸膜间皮细胞恶性转化中起重要作用。这些发现还为间皮瘤的治疗提供了新颖的思路和参考，并为纳米材料从业者的职业安全提供了选择。