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Grp78 调节 NLRP3 炎症小体并参与干燥综合征的发生。

Grp78 regulates NLRP3 inflammasome and participates in Sjogren's syndrome.

机构信息

Department of Rheumatology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Department of Rheumatology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Int Immunopharmacol. 2024 Oct 25;140:112815. doi: 10.1016/j.intimp.2024.112815. Epub 2024 Jul 31.

Abstract

OBJECTIVE

The purpose of the present study was to potential effects of forsythiaside A (FA) on Sjogren's syndrome (SS).

METHODS

Enzyme linked immunosorbent assay for detecting cytokines and Western blotting was used for detecting related protein expression.

RESULTS

FA effectively reduced the secretion of inflammatory cytokines, the expression of Caspase-1 and NLRP3 proteins and the expression of p65 in SS. FA also effectively inhibited the high expression of Grp78 in SS. When Grp78 expression was silenced, it effectively reduced the secretion of inflammatory cytokines, the expression of Caspase-1 and NLRP3 proteins and the expression of p65 in the nucleus in SS. FA effectively inhibit the secretion of inflammatory cytokines induced by overexpression of Grp78, the expression of Caspase-1 and NLRP3 proteins and the expression of p65 in the nucleus in SS.

CONCLUSION

FA induces the degradation of Grp78 protein, regulates the NF-κB signaling pathway in SS and inhibited NLRP3 inflammasome activation and reduced the release of inflammatory cytokines to alleviate SS.

摘要

目的

本研究旨在探讨连翘酯苷 A(FA)对干燥综合征(SS)的潜在作用。

方法

采用酶联免疫吸附法检测细胞因子,Western blot 检测相关蛋白表达。

结果

FA 可有效降低 SS 中炎症细胞因子的分泌、Caspase-1 和 NLRP3 蛋白的表达以及 p65 的核转位。FA 还可有效抑制 SS 中 Grp78 的高表达。沉默 Grp78 表达后,SS 中炎症细胞因子的分泌、Caspase-1 和 NLRP3 蛋白的表达以及 p65 的核转位均明显减少。FA 可有效抑制 Grp78 过表达诱导的炎症细胞因子分泌、Caspase-1 和 NLRP3 蛋白的表达以及 p65 的核转位。

结论

FA 可诱导 Grp78 蛋白降解,调节 SS 中的 NF-κB 信号通路,抑制 NLRP3 炎性小体激活,减少炎症细胞因子释放,从而缓解 SS。

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