Open Access

Hypoxia modifies the polarization of macrophages and their inflammatory microenvironment, and inhibits malignant behavior in cancer cells

  • Authors:
    • Xixian Ke
    • Cheng Chen
    • Yongxiang Song
    • Qingyong Cai
    • Jian Li
    • Yang Tang
    • Xu Han
    • Wendong Qu
    • Anping Chen
    • Hui Wang
    • Gang Xu
    • Daxing Liu
  • View Affiliations

  • Published online on: October 3, 2019     https://doi.org/10.3892/ol.2019.10956
  • Copyright: © Ke et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophages are a heterogeneous group of phagocytes that play critical roles in inflammation, infection and tumor growth. Macrophages respond to different environmental factors and are thereby polarized into specialized functional subsets. Although hypoxia is an important environmental factor, its impact on human macrophage polarization and subsequent modification of the inflammatory microenvironment have not been fully established. The present study aimed to elucidate the effect of hypoxia exposure on the ability of human macrophages to polarize into the classically activated (pro‑inflammatory) M1, and the alternatively activated (anti‑inflammatory) M2 phenotypes. The effect on the inflammatory microenvironment and the subsequent modification of A549 lung carcinoma cells was also investigated. The presented data show that hypoxia promoted macrophage polarization towards the M2 phenotype, and modified the inflammatory microenvironment by decreasing the release of proinflammatory cytokines. Modification of the microenvironment by proinflammatory M1 macrophages under hypoxia reversed the inhibition of malignant behaviors within the proinflammatory microenvironment. Furthermore, it was identified p38 signaling (a major contributor to the response to reactive oxygen species generated by hypoxic stress), but not hypoxia‑induced factor, as a key regulator of macrophages under hypoxia. Taken together, the data suggest that hypoxia affects the inflammatory microenvironment by modifying the polarization of macrophages, and thus, reversing the inhibitory effects of a proinflammatory microenvironment on the malignant behaviors of several types of cancer cell.

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Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Ke, X., Chen, C., Song, Y., Cai, Q., Li, J., Tang, Y. ... Liu, D. (1899). Hypoxia modifies the polarization of macrophages and their inflammatory microenvironment, and inhibits malignant behavior in cancer cells. Oncology Letters, 0, 0-0. https://doi.org/10.3892/ol.2019.10956
MLA
Ke, X., Chen, C., Song, Y., Cai, Q., Li, J., Tang, Y., Han, X., Qu, W., Chen, A., Wang, H., Xu, G., Liu, D."Hypoxia modifies the polarization of macrophages and their inflammatory microenvironment, and inhibits malignant behavior in cancer cells". Oncology Letters 0.0 (1899): 0-0.
Chicago
Ke, X., Chen, C., Song, Y., Cai, Q., Li, J., Tang, Y., Han, X., Qu, W., Chen, A., Wang, H., Xu, G., Liu, D."Hypoxia modifies the polarization of macrophages and their inflammatory microenvironment, and inhibits malignant behavior in cancer cells". Oncology Letters 0, no. 0 (1899): 0-0. https://doi.org/10.3892/ol.2019.10956