TRIM31 inhibits NLRP3 inflammasome and pyroptosis of retinal pigment epithelial cells through ubiquitination of NLRP3
TRIM31 inhibits NLRP3 inflammasome and pyroptosis of retinal pigment epithelial cells through ubiquitination of NLRP3
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DOI：
10.1002/cbin.11429
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发表时间：
2020-08-05
影响因子：
3.9
通讯作者：
Feng，Jingyang
中科院分区：
文献类型：
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作者：
Huang，Peirong;Liu，Wenjia;Feng，Jingyang
NOD样受体蛋白3（NLRP 3）与年龄相关性黄斑变性（AMD）有关。视网膜色素上皮（RPE）细胞作为黄斑的免疫防御细胞，其功能障碍导致AMD的临床相关变化。在本研究中，氧化低密度脂蛋白（ox-LDL）激活人RPE细胞系ARPE-19中的NLRP 3炎性体。我们的数据显示，ox-LDL显著增加ARPE-19细胞中NLRP 3、白细胞介素-1 β（IL-1β）和caspase-1的表达以及IL-1β的释放，而添加NLRP 3抑制剂INF 39剂量依赖性地逆转了ox-LDL的作用。过表达含有三重基序的蛋白31（TRIM 31）也抑制了ARPE-19细胞中ox-LDL的作用。TRIM 31敲低与ox-LDL具有相似的作用，但INF 39可阻断TRIM 31敲低的作用。此外，TRIM 31可以与ARPE-19细胞中的NLRP 3相互作用。TRIM 31的过表达增加NLRP 3泛素化。总之，结果表明TRIM 31可以增强NLRP 3泛素化，从而抑制人RPE细胞中的NLRP 3炎性小体和焦亡。
NOD‐like receptor protein 3 (NLRP3) is associated with age‐related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells serve as the immune defense of macula, and their dysfunction causes clinically relevant changes in AMD. In the present study, oxidized low‐density lipoprotein (ox‐LDL) activated the NLRP3 inflammasome in human RPE cell line ARPE‐19. Our data showed that the expression of NLRP3, interleukin‐1β (IL‐1β), and caspase‐1 and the release of IL‐1β in ARPE‐19 cells were substantially increased by ox‐LDL, whereas the addition of NLRP3 inhibitor INF39 dose‐dependently reversed the effect of ox‐LDL. Overexpression of tripartite motif‐containing protein 31 (TRIM31) also suppressed the effect of ox‐LDL in ARPE‐19 cells. TRIM31 knockdown had similar effects with ox‐LDL but INF39 could block the effect of TRIM31 knockdown. Moreover, TRIM31 could interact with NLRP3 in ARPE‐19 cells. Overexpression of TRIM31 increased NLRP3 ubiquitination. In conclusion, the results propose that TRIM31 could enhance NLRP3 ubiquitination, therefore inhibiting NLRP3 inflammasome and pyroptosis in human RPE cells.