Tripartite motif-containing 22 (TRIM22) has been documented to participate in numerous cellular activities during human diseases. However, whether TRIM22 is involved in the regulation of neuronal survival during the progression of cerebral ischemia/reperfusion (I/R) injury remains unknown. In the present study, treatment of HCN-2 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) markedly upregulated TRIM22 expression. A significant increase in TRIM22 expression was observed in the ischemic cortex tissues from middle cerebral artery occlusion/reperfusion mice. OGD/R inhibited the viability and induced the apoptosis of HCN-2 cells, which was accompanied by an increase in caspase-3 activity and an increase in LDH release. Furthermore, OGD/R increased the levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemoattractant protein-1 and induced NLRP3 inflammasome activation, as evidenced by increases in NACHT, LRR and PYD domains-containing protein 3, apoptosis-associated speck-like protein containing a caspase recruitment domain and cleaved caspase-1 expression and caspase-1 activity. However, these changes induced by OGD/R were blocked by silencing of TRIM22. In addition, TRIM22 regulated NF-κB activity in HCN-2 cells undergoing OGD/R stimulation. Furthermore, inhibition of NF-κB by pyrrolidine dithiocarbamate inhibited OGD/R-induced NLRP3 inflammasome activation in HCN-2 cells. Taken together, silencing of TRIM22 protects neurons against OGD/R-induced apoptosis and inflammation. The anti-inflammatory effect of TRIM22 knockdown was the consequence of inhibition of NF-κB/NLRP3 axis. TRIM22 may be a potential target for treating cerebral I/R injury.

中文翻译：

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敲除 TRIM22 通过抑制 NF-κB/NLRP3 轴缓解氧-葡萄糖剥夺/再氧合诱导的细胞凋亡和炎症。

已证明含有三方基序的 22 (TRIM22) 参与人类疾病期间的多种细胞活动。然而，TRIM22 是否参与脑缺血/再灌注 (I/R) 损伤进展过程中神经元存活的调节仍然未知。在本研究中，用氧-葡萄糖剥夺/复氧 (OGD/R) 处理 HCN-2 细胞显着上调 TRIM22 表达。在大脑中动脉闭塞/再灌注小鼠的缺血皮层组织中观察到 TRIM22 表达的显着增加。OGD/R抑制HCN-2细胞的活力并诱导其凋亡，伴随着caspase-3活性的增加和LDH释放的增加。此外，OGD/R 增加了肿瘤坏死因子-α、白细胞介素 (IL)-1 β、IL-6、和单核细胞趋化蛋白-1 并诱导 NLRP3 炎症小体激活，如 NACHT、LRR 和 PYD 结构域蛋白 3、凋亡相关斑点样蛋白（包含半胱天冬酶募集结构域和裂解的半胱天冬酶 1 表达和半胱天冬酶 1）的增加所证明活动。然而，这些由 OGD/R 引起的变化被 TRIM22 的沉默所阻止。此外，TRIM22 调节经历 OGD/R 刺激的 HCN-2 细胞中的 NF-κB 活性。此外，吡咯烷二硫代氨基甲酸酯对 NF-κB 的抑制抑制了 HCN-2 细胞中 OGD/R 诱导的 NLRP3 炎性体激活。总之，TRIM22 的沉默保护神经元免受 OGD/R 诱导的细胞凋亡和炎症。TRIM22 敲低的抗炎作用是抑制 NF-κB/NLRP3 轴的结果。