Tan Yan, Tan Si-Wei, Fan Bo-Ya, Li Lei, Zhou Yuan-Guo
Molecular Biology Center; State Key Lab of Trauma, Burns and Combined Injury; Research Institute of Surgery and Daping Hospital, Army Medical University, Chongqing, China.
Iran J Immunol. 2018 Jun;15(2):122-132.
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.
To investigate whether or not hemin regulates microglia-mediated secondary injury through activating the NLRP3/caspase-1 signaling pathway in microglia.
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.
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.
Hemin is a potential sterile danger signal molecule that can induce inflammasome activation without directly mediating inflammation damage on microglia.
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。
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。
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。
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。
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。