M2 Polarization of Macrophages Facilitates Arsenic-Induced Cell Transformation of Lung Epithelial Cells

Authors

Jiajun Cui, University of Kentucky
Wenhua Xu, University of KentuckyFollow
Jian Chen, Xiamen University, China
Hui Li, University of KentuckyFollow
Lu Dai, University of Kentucky
Jacqueline A. Frank, University of KentuckyFollow
Shaojun Peng, Yichun University, China
Siying Wang, Anhui Medical University, China
Gang Chen, University of KentuckyFollow

Abstract

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.

Document Type

Article

Publication Date

2-9-2017

Notes/Citation Information

Published in Oncotarget, v. 8, no. 13, p. 21398-21409.

This article is licensed under a Creative Commons Attribution 3.0 License.

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.15232

Funding Information

This work was supported by the American Cancer Society [RSG-11-116-01-CNE to G.C.], National Natural Science Foundation of China (No.31660325 to J.C.) and NCI Cancer Center Support Grant (P30 CA177558).

Repository Citation

Cui, Jiajun; Xu, Wenhua; Chen, Jian; Li, Hui; Dai, Lu; Frank, Jacqueline A.; Peng, Shaojun; Wang, Siying; and Chen, Gang, "M2 Polarization of Macrophages Facilitates Arsenic-Induced Cell Transformation of Lung Epithelial Cells" (2017). Pharmacology and Nutritional Sciences Faculty Publications. 63.
https://uknowledge.uky.edu/pharmacol_facpub/63