收稿日期: 2023-08-10
网络出版日期: 2024-04-19
基金资助
国家自然科学基金项目(82060399);广西自然科学基金项目(2023GXNSFDA026050);广西医学高层次人才培养“139”计划(［2020］15)
Short⁃chain fatty acids alleviate γδT cell⁃mediated inflammatory response via inhibiting IL⁃17A and NF⁃κB signaling pathway
Received date: 2023-08-10
Online published: 2024-04-19
目的 探究短链脂肪酸减轻γδT细胞介导炎症反应的作用机制。 方法 使用一定浓度的短链脂肪酸干预大鼠肠道来源的γδT细胞，CCK-8检测短链脂肪酸对γδT活性的影响，酶联免疫吸附测定（ELISA）检测白细胞介素17A（IL-17A）因子含量，实时荧光定量（RT-qPCR）检测IL-17A因子的表达水平，流式细胞仪分析IL-17+γδT细胞的比例，Western blot研究γδT细胞IL-17A和核转录因子κB（NF-κB）信号通路的影响。 结果 CCK-8结果提示乙酸钠的浓度≤ 0.5 mmol/L，丙酸钠、丁酸钠和混合短链脂肪酸的浓度≤ 0.25 mmol/L对γδT细胞的增殖无抑制作用（P > 0.05）；ELISA和RT-qPCR结果显示，丙酸钠、丁酸钠及混合短链脂肪酸处理的γδT细胞IL-17A的含量较Control组均显著降低。流式细胞检测结果示IL-17+γδT细胞的比例在丙酸钠、丁酸钠、混合短链脂肪酸及TSA干预下均明显下降（P < 0.001）；Western blot检测发现丙酸钠、丁酸钠和混合短链脂肪酸可抑制IL-17A、IKK的表达及NF-κB磷酸化水平（P < 0.05）。 结论 短链脂肪酸能抑制γδT细胞IL-17A和NF-κB信号通路的激活，从而减轻机体的炎症反应。
刘槃 , 席德双 , 黄瑞 , 滕益霖 , 刘睿 , 曾高峰 , 宗少晖 . 短链脂肪酸通过抑制白细胞介素17A和NF-κB信号通路减轻γδT细胞介导的炎症反应[J]. 实用医学杂志, 2024 , 40(8) : 1088 -1094 . DOI: 10.3969/j.issn.1006-5725.2024.08.012
Objective To explore the mechanism of short-chain fatty acids in alleviating γδT cell-mediated inflammatory response. Methods A certain concentration of short-chain fatty acids was used to intervene in rat intestinal-derived γδT cells. CCK-8 was used to detect the effect of shortchain fatty acids on γδT activity. ELISA was used to detect the content of the IL-17A， RT-qPCR was utilized to detect the expression of the IL-17A， and flow cytometry was applied to analyze the IL-17+γδT cell frequency. The effect of SCFAs on IL-17A and NF-κB signaling pathway in γδT cells were observed by Western blot. Results CCK-8 assay showed that the concentration of sodium acetate was less than or equal to 0.5 mmol/L， and the concentrations of sodium propionate， sodium butyrate， and mixed short-chain fatty acids were less than or equal to 0.25 mmol/L， indicating no inhibitory effect on the proliferation of γδT cells. ELISA and RT-qPCR showed that the treatment of γδT cells with sodium propionate， sodium butyrate， and mixed short-chain fatty acids significantly decreased the levels of IL-17A compared with the control group. Flow cytometry revealed a significant decrease in the proportion of IL-17+γδT cells under the treatment of sodium propionate， sodium butyrate， mixed shortchain fatty acids， and TSA intervention. Western blot found that sodium propionate， sodium butyrate， and mixed shortchain fatty acids could inhibit the expression of IL-17A and IKK， as well as the phosphorylation level of NF-κB. Conclusion Shortchain fatty acids could inhibit the activation of IL-17A and NF-κB signaling pathway in γδT cells， thereby alleviating the inflammatory response in the body.
Key words： short-chain fatty acids; γδT cell; IL-17A; NF-κB
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