Document Type: Original Article
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Institute of Surgery Research and Daping Hospital, Army Medical University, Chongqing, China
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
Department of Clinical Medicine, Shandong University, Jinan, China
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.