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血红素诱导N9小胶质细胞中NLRP3炎性小体的激活。

Hemin Induces the Activation of NLRP3 Inflammasome in N9 Microglial Cells.

作者信息

Tan Yan, Tan Si-Wei, Fan Bo-Ya, Li Lei, Zhou Yuan-Guo

机构信息

Molecular Biology Center; State Key Lab of Trauma, Burns and Combined Injury; Research Institute of Surgery and Daping Hospital, Army Medical University, Chongqing, China.

出版信息

Iran J Immunol. 2018 Jun;15(2):122-132.

Abstract

BACKGROUND

Hemin is an important sterile component that induces a neuroinflammatory response after intracerebral hemorrhage, in which NLRP3 inflammasome activation has also proved to be involved. Although microglial activation acts as a key contributor in the neuroinflammatory response, the relationship between hemin and NLRP3 in microglia remains poorly understood.

OBJECTIVE

To investigate whether or not hemin regulates microglia-mediated secondary injury through activating the NLRP3/caspase-1 signaling pathway in microglia.

METHODS

In this study, N9 microglial cells were treated with hemin, and subsequently used to detect the production of caspase-1 p10 and NLRP3 inflammasome assembly. An ELISA was subsequently performed to measure the secretion of IL-1β.

RESULTS

It was found that the production of activated caspase-1 was dose- and time-dependent with regards to hemin. Moreover, hemin was observed to be capable of inducing the assembly of the NLRP3 inflammasome without any increase in IL-1β. Similarly, the supernatant of hemin-treated primary microglial cells did not increase in IL-1β secretion. Furthermore, hemin-induced NLRP3 inflammasome activation did not significantly affect pyroptosis.

CONCLUSION

Hemin is a potential sterile danger signal molecule that can induce inflammasome activation without directly mediating inflammation damage on microglia.

摘要

背景

血红素是脑出血后诱导神经炎症反应的一种重要无菌成分,其中NLRP3炎性小体激活也已被证明参与其中。尽管小胶质细胞激活在神经炎症反应中起关键作用,但血红素与小胶质细胞中NLRP3之间的关系仍知之甚少。

目的

探讨血红素是否通过激活小胶质细胞中的NLRP3/半胱天冬酶-1信号通路来调节小胶质细胞介导的继发性损伤。

方法

在本研究中,用血红素处理N9小胶质细胞,随后用于检测半胱天冬酶-1 p10的产生和NLRP3炎性小体组装。随后进行酶联免疫吸附测定以测量白细胞介素-1β的分泌。

结果

发现活化的半胱天冬酶-1的产生在血红素方面呈剂量和时间依赖性。此外,观察到血红素能够诱导NLRP3炎性小体组装而白细胞介素-1β没有任何增加。同样,血红素处理的原代小胶质细胞的上清液中白细胞介素-1β分泌没有增加。此外,血红素诱导的NLRP3炎性小体激活对细胞焦亡没有显著影响。

结论

血红素是一种潜在的无菌危险信号分子,可诱导炎性小体激活而不直接介导对小胶质细胞的炎症损伤。

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