去泛素化酶USP14对炎症性肺部疾病模型中炎症反应因子的影响  

The effect of deubiquitinating enzyme USP14 on proinflammatory cytokines in Inflammatory lung diseases model

作　　者：王丹[1] 马奔卉 李聪[1] 李超[2] WANG Dan;MA Ben-hui;LI Cong(Department of Anesthesiology of The First Hospital of Jilin University,Jilin Changchun 130021,China)

机构地区：[1]吉林大学第一医院麻醉科,吉林长春130021 [2]吉林大学第一医院二部手术室,吉林长春130021

出　　处：《中国实验诊断学》2021年第7期1066-1070,共5页Chinese Journal of Laboratory Diagnosis

基　　金：国家自然科学基金资助项目(81800006)。

摘　　要：目的研究去泛素化酶USP14在炎症性肺部疾病中对炎性细胞因子的调节作用及探索USP14的小分子抑制剂IU1对炎性反应细胞的炎性消退作用。方法MLE12细胞过表达USP14或抑制USP14的表达后,通过LPS或TNF-α刺激细胞的方法产生炎症反应细胞模型,采用Western blot法检测IκB和USP14蛋白表达的变化情况,采用ELISA法检测炎性因子IL-6或KC及TNF-α的水平。结果与Vector相比,过表达USP14显著抑制了IκB蛋白水平表达(P<0.05),并且显著增加LPS或者TNF-α所诱导产生的炎性细胞因子IL-6的释放(P<0.05);与Sicont相比,基因敲除Usp14显著抑制了LPS或者TNF-α所诱导产生的IL-6的释放(P<0.05);预处理IU1显著抑制了LPS或者TNF-α所诱导产生的IL-6的释放并且显著抑制了LPS所诱导产生的KC及TNF-α释放(P<0.05)。结论USP14通过调节IκB的蛋白水平的表达影响炎症性肺部疾病模型中促炎因子的释放。明确了IU1的炎症消退作用。Objective To study the positive regulatory effect of deubiquitin enzyme USP14 on inflammatory cytokines in inflammatory lung disease.In addition,to study the inflammatory regression effect of IU1 on inflammatory response cells,a small molecule inhibitor of USP14.Methods After overexpression of USP14 or inhibition of USP14 expression in MLE12 cells,the inflammatory response cell model was generated by stimulating cells with LPS or TNF-α.The expression of IκB and USP14 were detected by Western blot,and the levels of inflammatory cytokines IL-6 or KC and TNF-αwere detected by ELISA.Results Compared with Vector,overexpression of USP14 significantly inhibited expression of IκB protein and significantly increased the release of LPS or TNF-α-induced inflammatory cytokine IL-6(P<0.05);Compared with Sicont,knockout USP14 significantly inhibited the release of IL-6 induced by LPS or TNF-α(P<0.05);Pretreatment of IU1 significantly inhibited the release of IL-6 induced by LPS or TNF-αand significantly inhibited LPS-induced KC and TNF-αrelease(P<0.05).Conclusion USP14 affects the release of proinflammatory cytokines in inflammatory pulmonary disease models by regulating the expression of IκB protein.In addition,the inflammatory regression effect of IU1 was confirmed.

关 键 词：脂多糖 肿瘤坏死因子 肺炎 泛素特异性蛋白酶14 细胞因子 

分 类 号：R563.1[医药卫生—呼吸系统]