title: Extremely low frequency magnetic fields regulate differentiation of regulatory T cells: Potential role for ROS-mediated inhibition on AKT.
abstract: Our previous studies showed that extremely low frequency magnetic fields (ELF-MFs) inhibited tumor growth and change proportion of splenic regulatory T cells (Treg cells). Here, we focus on the effect of ELF-MFs on lung metastatic melanoma mouse model and the regulatory mechanism of ELF-MFs on the differentiation of Treg cells. Tumor-bearing mice were exposed to sham ELF-MFs and ELF-MFs (0.4 T, 7.5 Hz) 2 h/day for 27 days. Metastatic tumor burden of lung was significantly decreased after ELF-MF treatment. Compared to the control group, expressions of matrix metalloproteinase (MMP2, MMP9) and forkhead box P3 (Foxp3) in lung nodules significantly decreased in the ELF-MF group. Moreover, in vitro, after stimulated with anti-CD3, anti-CD28 antibodies and transforming growth factor-β (TGF-β) and treated with ELF-MFs for 2 h, expression of Foxp3 in total T cells was significantly decreased. Differentiation rate of Treg cells was inhibited from 32.0% to 22.1% by ELF-MFs. Furthermore, reactive oxygen species (ROS) was increased and phospho-serine/threonine protein kinase (p-AKT) was inhibited in both T cells and Jurkat cells. ROS scavenger N-acetyl-l-cysteine reversed inhibition of AKT pathway and expression of Foxp3 from 18.6% to 26.6% in T cells. Taken together, our data show that ELF-MF exposure promoted the inhibitory effect of ROS on AKT pathway and decreased Foxp3 expression, which provides an explanation for why ELF-MF exposure can inhibit differentiation of Treg cells and enhance antitumor effect in metastatic melanoma mouse model.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Tang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Feiya
authors.initials: F
authors.lastname: Ma
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
authors.forename: Sunan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Laboratory of Solid State Microstructures, Nanjing University, Nanjing, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Du
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004789:Enzyme Activation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D060526:Magnetic Fields; D008545:Melanoma / Q000473:pathology; D051379:Mice; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT pathway; ELF-MFs; reactive oxygen species; treg cells