College of Animal Science and Technology, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, 471023, Henan, People's Republic of China.
School of Information Technology and Urban Construction, Luoyang Polytechnic, Keji Avenue 6, Yibin District, Luoyang, 471934, Henan, People's Republic of China.
Biol Trace Elem Res. 2021 Sep;199(9):3402-3410. doi: 10.1007/s12011-020-02464-6. Epub 2020 Nov 26.
C2C12 cells were cultured on medium containing fluoride (0, 1, and 2.5 mmol/L) for 48 h to investigate the effect of excessive fluoride on T helper 17 (Th17)-related cytokine expression profile in skeletal muscle cells, and the culture supernatant was collected and subjected for the detection of 18 cytokines via Th17 array. Results showed that compared with the control group, no differential expression proteins (DEPs) were found in the 1 mmol/L fluoride group; however, eight DEPs were upregulated in the 2.5 mmol/L fluoride group, including macrophage inflammatory protein-3α (MIP-3α), interleukin-21 (IL-21), IL-13, IL-17F, IL-28A, transforming growth factor type beta 1 (TGF-β1), IL-23, and IL-17A. In addition, five DEPs (MIP-3α, IL-13, IL-21, TGF-β1, and IL-17F) were upregulated in the 2.5 mmol/L fluoride group compared with the 1 mmol/L fluoride group. Gene ontology analysis revealed that the positive regulation of cytokine production, cytokine activity, receptor ligand activity, and cytokine receptor binding accounted for high percent of DEPs present. Kyoto Encyclopedia of Genes and Genomes analysis showed that these DEPs primarily involved 12 pathways enriched in the cytokine-cytokine receptor interaction and IL-17 signaling pathway after 2.5 mmol/L fluoride treatment. The results indicated that fluoride might induce cytotoxicity by disturbing Th17-related cytokine expression.
将 C2C12 细胞置于含有氟化物（0、1 和 2.5mmol/L）的培养基中培养 48 小时，以研究过量氟化物对骨骼肌细胞中辅助性 T 细胞 17（Th17）相关细胞因子表达谱的影响，并收集培养上清液，通过 Th17 阵列检测 18 种细胞因子。结果表明，与对照组相比，1mmol/L 氟化物组未发现差异表达蛋白（DEPs）；然而，在 2.5mmol/L 氟化物组中，有 8 种 DEPs 上调，包括巨噬细胞炎症蛋白-3α（MIP-3α）、白细胞介素-21（IL-21）、IL-13、IL-17F、IL-28A、转化生长因子-β1（TGF-β1）、IL-23 和 IL-17A。此外，与 1mmol/L 氟化物组相比，2.5mmol/L 氟化物组中还上调了 5 种 DEPs（MIP-3α、IL-13、IL-21、TGF-β1 和 IL-17F）。基因本体分析显示，细胞因子产生的正调控、细胞因子活性、受体配体活性和细胞因子受体结合占 DEPs 的高比例。京都基因与基因组百科全书分析显示，这些 DEPs 主要参与了 12 条通路，这些通路在 2.5mmol/L 氟化物处理后富集在细胞因子-细胞因子受体相互作用和 IL-17 信号通路中。结果表明，氟化物可能通过干扰 Th17 相关细胞因子的表达而引起细胞毒性。
