首页|Nurr1通过抑制小胶质细胞NF-κB发挥抗炎作用

Nurr1通过抑制小胶质细胞NF-κB发挥抗炎作用

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目的 探索在细菌脂多糖(LPS)诱导的小鼠小胶质细胞(BV2 细胞株)炎症反应中,核受体相关蛋白1(Nurr1)是否通过抑制NF-κB的表达及核转位发挥抗炎作用.方法 培养小鼠BV2 小胶质细胞株,将细胞分为Ctrl组、LPS组、C-DIM12(Nurrl特异性激动剂)组、siRNA干扰组、LPS+C-DIM12 组.利用CCK-8 检测LPS和C-DIM12 的最适作用浓度,用Western blot观察NF-κB和Nurr1 的表达变化,用酶联免疫吸附法(ELISA)检测培养液中炎症因子IL-6、IL-1β和TNF-α的水平,用免疫荧光观察siRNA干扰或C-DIM12 激活Nurr1 表达活性后,NF-κB及p-IκB 在 BV2 细胞中的表达水平.结果 LPS 刺激 BV2 细胞后,NF-κB 表达提高,炎症因子IL-1、IL-6、TNF-α释放量增加(P<0.05).C-DIM12 激活Nurr1 后,免疫荧光染色技术和Western blot实验结果都显示NF-κB的表达显著下降,而小干扰RNA(siNurr1)沉默Nurr1 表达后,NF-κB表达增加.在LPS激活的小胶质细胞中,NF-κB二聚体分子的结合分子p-IκB的磷酸化蛋白水平相对于对照组显著升高,而C-DIM12激活Nurr1 后,p-IκB水平显著下降.结论 Nurr1 可以通过抑制小胶质细胞NF-κB表达水平并阻止NF-κB核位移发挥抗炎作用.Nurr1 可能是一个新的潜在的治疗中枢神经系统炎症相关疾病的靶点.
Nurr1 attenuates microglia inflammation by inhibiting NF-κB
Objective To explore whether Nurr1 inhibits NF-κB expression and nuclear translocation in BV2 microglia inflam-matory response induced by LPS to play an anti-inflammatory role.Methods Mouse BV2 microglia cells were cultured and divided in-to Ctrl group,LPS group,C-DIM12 group(Nurr1 specific agonist),siRNA interference group and LPS+C-DIM12 group.CCK-8 was used to detect the optimal concentration of LPS and C-DIM12,and the expression changes of NF-κB and Nurr1 were measured by Western blot,and the inflammatory factors IL-6,IL-1β and TNF-α levels were detected by ELISA.After the expression activity of Nurr1 was disrupted by siRNA or activated by C-DIM12,the expression levels of NF-κB and p-IκB in BV2 cells were investigated.Results After the BV2 cells were stimulated by LPS,the expression of NF-κB increased and the release of inflammatory factors IL-1,IL-6,TNF-α also increased(P<0.05).After Nurr1 was activated by C-DIM12,the expression of NF-κB decreased signif-icantly.However,after small interfering RNA(siNurr1)silenced the expression of Nurr1,the expression of NF-κB increased.In LPS-activated microglia,the level of phosphorylated protein I-κB,which was NF-κB dimer molecule binding molecule,was significantly higher than that in the control group.After Nurr1 was activated by C-DIM12,pI-κB level decreased significantly.Conclusion Nurr1 can inhibit the expression of NF-κB,reverse NF-κB nuclear translocation and protect the CNS from inflammation.Nurr1 may be a new and potential target for the treatment of inflammation related CNS diseases.

Nurr1NF-κBNeuroinflammationMicrogliap-IκB

王伟、侯晓霖、陈秋元、潘晓玥、彭涛、王俊燕、李云鸿、王银

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宁夏医科大学总医院,宁夏 银川 750004

宁夏医科大学基础医学院,宁夏 银川 750004

Nurr1 NF-κB 神经炎症 小胶质细胞 p-IκB

国家自然科学基金宁夏回族自治区自然科学基金宁夏回族自治区自然科学基金宁夏回族自治区重点研发基金

820602232022AAC036072021AAC033722021BEG03097

2024

宁夏医学杂志
中华医学会宁夏分会

宁夏医学杂志

影响因子:0.706
ISSN:1001-5949
年,卷(期):2024.46(4)
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