Iranian Journal of Immunology

Hemin Induces the Activation of NLRP3 Inflammasome in N9 Microglial Cells

Document Type : Original Article

Authors

Yan Tan 1, 2
Si-Wei Tan 1
Bo-Ya Fan 3
Lei Li 2
Yuan-Guo Zhou 1

1 Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Institute of Surgery Research and Daping Hospital, Army Medical University, Chongqing, China

2 Department of Infection and Immunity, State Key Laboratory of Trauma, Burn, and Combined Injury, Institute of Surgery Research and Daping Hospital, Army Medical University, Chongqing, China

3 Department of Clinical Medicine, Shandong University, Jinan, China

https://doi.org/10.22034/iji.2018.39376
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.

Keywords

Caspase-1
Hemin
Microglia
NLRP3 Inflammasome
Iranian Journal of Immunology
Volume 15, Issue 2
Spring 2018
Pages 122-132

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