M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells
Metrics: PDF 2031 views | HTML 2975 views | ?
Jiajun Cui1,2,*, Wenhua Xu2,3,*, Jian Chen4,*, Hui Li2, Lu Dai5, Jacqueline A. Frank2, Shaojun Peng1, Siying Wang6, Gang Chen2
1Department of Biochemistry, Medical College of Yichun University, Yichun, Jiangxi 336000, China
2Department Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, USA
3Department of Neurology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, China
4Department of Ultrasound, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361001, China
5Department of Toxicology & Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
6Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China
*These authors have contributed equally to this work
Jiajun Cui, email: [email protected]
Gang Chen, email: [email protected]
Keywords: macrophage, lung cancer, arsenic, transformation
Received: July 13, 2016 Accepted: January 16, 2017 Published: February 09, 2017
The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.