文献类型：期刊文献

英文题名：Formaldehyde promotes tumor-associated macrophage polarizations and functions through induction of HIF-1α-mediated glycolysis

作者：Shu, Qi[1,2];Ma, Huijuan[1,2];Wang, Tingqian[1,2];Wang, Peiyao[1,2];Xu, Huan[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2023

卷号：390

起止页码：5

外文期刊名：TOXICOLOGY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001112314400001)】；

基金：Acknowledgements This work was funded by National Natural Science Foundation of China [grant No. 42177417] . This work was also funded by Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) .

语种：英文

外文关键词：Formaldehyde; Tumor-associated macrophage; Glycolytic metabolism; HIF-1 alpha; T cell suppression; Tumor cell proliferation

摘要：Formaldehyde (FA) exposure has been positively correlated with many diseases including various types of cancers. However, the mechanisms of FA-related carcinogenesis are still unclear. Tumor-associated macrophages (TAMs) are the most abundant immune cells in tumor microenvironment, which is a heterogeneous population consist of both pro-inflammatory (M1) and immunosuppressive (M2) cells. TAMs are deeply involved in tumor development and progression. Our previous studies demonstrated that FA enhanced M1 polarization of macrophages through induction of HIF-1 alpha-mediated glycolysis. To examine if TAM polarizations are also potentiated by FA, BALB/c nude mice were inoculated with A549 cells to develop subcutaneous tumors and exposed to 2.0 mg/m(3) FA for 14 days. Significant increases of both M1 and M2 polarizations of TAMs were observed in tumor tissues of FA-exposed mice. After confirmation of the potentiation effects in RAW264.7 and THP-1-derived in vitro TAM models, FA at 25 and 50 11M was found to enhance TAM immunosuppressive functions and glycolytic metabolism. In addition, FA-induced glycolysis in TAMs was reversed by a specific HIF-1 alpha inhibitor PX-478 at 5 11M, and suppression of glycolytic metabolism with a glucose analog 2-DG at 1 mM also alleviated FA-potentiated TAM functions, which indicated that FA induced TAM polarizations through the upregulation of HIF-1 alpha-mediated glycolysis. These results illustrated a potential carcinogenic mechanism of FA through metabolic disturbance of tumor immunity, which could be utilized to develop preventative or therapeutic agents for FA-induced carcinogenesis and immune disorders.