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TRIM21 causes abnormal expression of IL-6 in oral lichen planus via the TRIB2-MAPK signal axis
Chenyan Jiang1,2,3,4,5,6, Wei Wei7, Yufeng Wang1,2,3
1Department of Oral Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine Shanghai 200011, China.
Abstract:
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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