β-arrestin-2靶向NF-κB通路抑制类风湿性关节炎中FLSs的炎性反应  

Inhibitory Effect ofβ-arrestin-2 on Inflammatory Response of FLSs in Rheumatoid Arthritis by Targeting NF-κB Pathway

作　　者：曹峰 黄承 程继伟 余霄 CAO Feng;HUANG Cheng;CHENG Jiwei(Ningbo University School of Medicine,Graduate School,Zhejiang 315211,China)

机构地区：[1]宁波大学医学院研究生院,315211 [2]中国人民解放军联勤保障部队第九〇六医院骨科,315040 [3]中国科学院大学宁波华美医院骨科,315000

出　　处：《医学研究杂志》2022年第1期88-93,共6页Journal of Medical Research

基　　金：浙江省医药卫生科技计划项目(2018Ky156);浙江省宁波市自然科学基金资助项目(2019A610248)。

摘　　要：目的明确β-arrestin-2影响NF-κB通路调节FLS炎性反应的作用。方法通过构建小鼠CIA模型,分离获取RA-FLSs细胞,qRT-PCR法检测IL-1β、IL-6的表达情况;Western blot法检测MMP3、MMP13、p-P65、p-IκBα的表达情况;使用NF-κB通路抑制剂BAY 11-7082刺激RA-FLSs细胞,分析细胞炎性因子、软骨基因表达情况。结果qRT-PCR结果显示IL-1β、IL-6的表达水平显著降低,过表达β-arrestin-2可以降低RA-FLSs细胞中炎性因子水平;Western blot法结果显示,β-arrestin-2能够降低软骨基因MMP3、MMP13、p-P65和p-IκBα的表达水平,抑制NF-κB的活性;BAY 11-7082与β-arrestin-2联合刺激RA-FLSs后,炎性因子与软骨基因的表达量进一步降低。结论β-arrestin-2靶向NF-κB通路,降低炎性因子、软骨基因的表达,抑制NF-κB信号通路的活化,调节RA-FLSs的炎性反应。Objective To clarify the effect ofβ-arrestin-2 on NF-κB pathway in regulating FLS inflammatory response.Methods RA-FLSs cells were isolated by constructing mouse CIA model,and the expressions of IL-1βand IL-6 were detected by qRT-PCR.The expression of MMP3 and MMP13 was detected by Western blot.Western blot was used to detect the expression of p-P65 and p-IκBαin NF-κB signaling pathway.NF-κB pathway inhibitor BAY 11-7082 was used to stimulate RA-FLSs cells to analyze the expression of inflammatory factors and cartilage genes.Results qRT-PCR results showed that the expression levels of IL-1βand IL-6 were significantly reduced,and the overexpression ofβ-arrestin-2 could reduce the level of inflammatory factors in RA-FLSs cells.Western blot results showed thatβ-arrestin-2 could reduce the expression levels of cartilage genes MMP3,MMP13,p-P65 and p-IκBα,and inhibit the activity of NF-κB.After RA-FLSs were stimulated with BAY 11-7082 andβ-arrestin-2,the expression of inflammatory factors and cartilage genes were further decreased.Conclusionβ-arrestin-2 targets NF-κB pathway,reduces the expression of inflammatory factors and cartilage genes,inhibits the activation of NF-κB signaling pathway,and regulates the inflammatory response of RA-FLSs.

关 键 词：类风湿性关节炎 β-arrestin-2 NF-ΚB 成纤维样滑膜细胞 

分 类 号：R593.22[医药卫生—内科学]