Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA.
Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, USA.
Toxicol Appl Pharmacol. 2022 Nov 15;455:116265. doi: 10.1016/j.taap.2022.116265. Epub 2022 Oct 5.
Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium [Cr(VI)], which is used in multiple settings, resulting in widespread environmental and occupational exposures as well as heavy use. The mechanism by which Cr(VI) causes lung cancer is not completely understood. Currently, it is admitted chromosome instability is a key process in the mechanism of Cr(VI)-induced cancer, and previous studies have suggested Cr(VI) impacts the lung tissue in mice by triggering tissue damage and inflammation. However, the mechanism underlying Cr(VI)-induced inflammation and its exact role in lung cancer are unclear. Therefore, this review aimed to systematically examine previous studies assessing Cr(VI)-induced inflammation and to summarize the major inflammatory pathways involved in Cr(VI)-induced inflammation. In cell culture studies, COX2, VEGF, JAK-STAT, leukotriene B4 (LTB4), MAPK, NF-ҡB and Nrf2 signaling pathways were consistently upregulated by Cr(VI), clearly demonstrating that these pathways are involved in Cr(VI)-induced inflammation. In addition, Akt signaling was also shown to contribute to Cr(VI)-induced inflammation, although discrepant findings were reported. Few mechanistic studies were performed in animal models, in which Cr(VI) upregulated oxidative pathways, NF-kB signaling and the MAPK pathway in the lung tissue. Similar to cell culture studies, opposite effects of Cr(VI) on Akt signaling were reported. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation. However, discrepant findings and other major issues in study design, both in cell and animal models, suggest that further studies are required to unveil the mechanism of Cr(VI)-induced inflammation and its role in lung cancer.
除了吸烟，肺癌还可能由其他因素引起，包括重金属如镉、镍、砷、铍和六价铬（Cr(VI)），这些金属被广泛应用于多种环境和职业暴露，导致其大量使用。Cr(VI)导致肺癌的机制尚不完全清楚。目前，公认染色体不稳定性是 Cr(VI)致癌机制中的一个关键过程，先前的研究表明 Cr(VI)通过引发组织损伤和炎症来影响小鼠的肺组织。然而，Cr(VI)诱导的炎症的机制及其在肺癌中的确切作用尚不清楚。因此，本综述旨在系统地评估以前评估 Cr(VI)诱导的炎症的研究，并总结涉及 Cr(VI)诱导的炎症的主要炎症途径。在细胞培养研究中，Cr(VI)一致地上调了 COX2、VEGF、JAK-STAT、白三烯 B4 (LTB4)、MAPK、NF-ҡB 和 Nrf2 信号通路，这清楚地表明这些途径参与了 Cr(VI)诱导的炎症。此外，Akt 信号也被证明有助于 Cr(VI)诱导的炎症，尽管有报道称存在不一致的发现。在动物模型中进行的机制研究很少，其中 Cr(VI)在上皮组织中上调了氧化途径、NF-kB 信号和 MAPK 途径。与细胞培养研究类似，Cr(VI)对 Akt 信号的相反影响也有报道。这项工作为 Cr(VI)诱导肺炎症的机制提供了深入的了解。然而，细胞和动物模型中的不一致发现和其他主要研究设计问题表明，需要进一步的研究来揭示 Cr(VI)诱导的炎症机制及其在肺癌中的作用。
