AUTHORS:
Yaohua Zhuang School of Public Health, Anhui University of Science and Technology, Hefei, China
Peng Gao School of Public Health, Anhui University of Science and Technology, Hefei, China
Hangbing Cao School of Public Health, Anhui University of Science and Technology, Hefei, China
Yujing Wang School of Public Health, Anhui University of Science and Technology, Hefei, China
Wanjing Xing School of Public Health, Anhui University of Science and Technology, Hefei, China
Huan Xu School of Public Health, Anhui University of Science and Technology, Hefei, China
Min Mu School of Public Health, Anhui University of Science and Technology, Hefei, China
Dongqing Ye School of Public Health, Anhui University of Science and Technology, Hefei, China

ABSTRACT:
Methylglyoxal (MGO) is a widely-used compound in food industry, which is also produced by glycolytic metabolism. It is known to be associated with multiple chronic diseases, such as type 2 diabetes, cardiovascular diseases, and cancers. Although our immune system is actively removing mutated cells, recent findings indicated that tumor-associated macrophages (TAMs) could induce immunosuppression and promote cancer cell proliferation in tumor microenvironment, the polarization of which was regulated by cell metabolism. Since the MGO levels can be increased by the accelerated glycolysis in tumor microenvironment, the impacts of MGO on TAM polarization should be examined to reveal its potential immunotoxicity. In the present study, the polarization of THP-1-derived macrophages to M2d-like TAMs was found to be promoted by MGO at 50 to 200 µM. The M2d phenotypes and the immunosuppressive functions were found to be induced by MGO during polarization. MGO was also found to increase AMPK phosphorylation in the M2d-like TAM model and the MGO-promoted polarization was also found to be reversed by an AMPK inhibitor. Collectively, these results not only demonstrated that MGO could potentiate AMPK-mediated polarization of M2d-like TAMs, but also indicated that the AMPK pathway might be utilized as a therapeutic target for MGO-induced immunotoxicity.

Keywords: Methylglyoxal, Tumor-Associated Macrophages, AMPK, M2d Polarization, Immunosuppression, Tumor Microenvironment

Conference Venue: Male, Maldives
Conference Date: 5-7 November 2024

ISBN Number: 978-625-00-7517-3
DOI Number: https://doi.org/10.53375/imhsc.2024.114


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