TRIM21 causes abnormal expression of IL-6 in oral lichen planus via the TRIB2-MAPK signal axis.

TRIM21 causes abnormal expression of IL-6 in oral lichen planus via the TRIB2-MAPK signal axis.
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TRIM21 通过 TRIB2-MAPK 信号轴导致口腔扁平苔藓中 IL-6 的异常表达。

DOI:
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发表时间:
2020-08
影响因子:
2.2
通讯作者:
Guoyao Tang
Guoyao Tang
中科院分区:
医学4区
文献类型:
--
作者:
Chenyan Jiang;Wei Wei;Yufeng Wang;Chencheng Song;Lei Pan;Kai Sun;Guanhuan Du;Yiwen Deng;Guoyao Tang

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口腔扁平苔藓(Oral lichen planus,OLP)是口腔常见的慢性炎症性疾病,有发展为口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的危险。因此,有必要进一步研究TRIM 21在OLP发病中的作用及其机制。 方法 Western blot和qPCR检测TRIM 21对ERK、p-ERK、AP-1、IL-6、TRIB 2、IRF 3和IRF 7细胞水平的影响,同时进行免疫共沉淀以验证Trim 21和TRIB 2蛋白之间的相互作用。还使用ELISA评估TRIM 21对T细胞中的TH 1/TH 2平衡的影响。 结果 Western blot结果显示,TRIM 21过表达可显著增加H9细胞p-ERK、c-fos、c-jun、IL-6和TRIB 2的表达(P<0.01和P<0.001),而抑制IRF 3和IRF 7的表达(P<0.05)。另一方面,TRIM 21不调节ERK的磷酸化以及AP-1和TRIB 2的mRNA表达。TRIM 21与TRIB 2-ERK的蛋白酶体降解有关。TRIM 21不仅通过抑制TRIB 2的泛素化,还通过ERK途径影响IL-6来调节TRIB 2的水平。 结论 TRIM 21通过调节TRIB 2-MAPK信号轴,导致OLP中IL-6的异常表达,从而导致T淋巴细胞Th 1/Th 2平衡紊乱。
Oral lichen planus (OLP) is a common chronic inflammatory disease in the oral cavity, and has the risk of developing into oral squamous cell carcinoma (OSCC). It is necessary to discover the role of TRIM21 in the pathogenesis of OLP and its underlying mechanism. METHODS Western bolt and qPCR assays were used to detect the effects of TRIM21 on cellular levels of ERK, p-ERK, AP-1, IL-6, TRIB2, IRF3, and IRF7, while co-immunoprecipitation was performed to verify the interaction between Trim21 and TRIB2 protein. The TRIM21 effect on TH1/TH2 balance in T cells was also evaluated using ELISA. RESULTS The results of western blot showed that TRIM21 overexpression significantly increased p-ERK, c-fos, c-jun, IL-6 and TRIB2 levels in H9 cells (P<0.01 and P<0.001), however, inhibited the IRF3 and IRF7 levels (P<0.05). On the other hand, TRIM21 did not regulate the phosphorylation of ERK and the mRNA expression of AP-1 and TRIB2. In addition, TRIM21 was in relation to the proteasome degradation in TRIB2-ERK. TRIM21 also regulated the level of TRIB2 not only by inhibiting the ubiquitination of TRIB2, but also by affecting IL-6 through the ERK pathway. CONCLUSION TRIM21 caused abnormal expression of IL-6 in OLP via regulating TRIB2-MAPK signal axis, leading to the disrupted Th1/Th2 balance in T lymphocytes.
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