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Biochem Biophys Res Commun. 2019 Jul 5;514(4):1066-1073. doi: 10.1016/j.bbrc.2019.05.033. Epub 2019 May 13.

CYLD deficiency exacerbates lipopolysaccharide (LPS)-induced pyroptosis in astrocytes of mice with sepsis.

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Department of Inpatient Ward 2, The Third People's Hospital of Huzhou, Huzhou, 313000, China.
Psychosomatic Department, Chang'an Hospital, Xi'an, 710016, China.
Psychiatry Department, Wenzhou Seventh People's Hospital, Wenzhou, 325000, China. Electronic address:


Sepsis is a clinical syndrome occurring in patients following infection or injury, and is a leading cause of mortality in the world. However, the pathogenesis that contributes to sepsis and its associated brain injury is still unclear. Cylindromatosis (CYLD) is integrally involved in various physiological processes, such as immune responses, inflammation and cell cycle control. In the study, in vitro and in vivo models with sepsis by lipopolysaccharide (LPS) were performed to investigate the role of CYLD in inflammasome and its related astrocyte (AST) pyroptosis. The in vitro results suggested that LPS treatment significantly resulted in inflammasome activation and pyroptosis in AST. CYLD expression was progressively degraded upon LPS incubation in AST. Importantly, CYLD knockout (KO) could further promote pyroptosis and accelerate histone release in LPS-stimulated AST. In addition, the in vivo experiments suggested that LPS treatment in mice enhanced Caspase-1 immunoreactivity and resulted in high expression of phosphorylated nuclear factor-κB p65 (NF-κB p65), interleukin-1β (IL-1β) and IL-18 in hippocampus tissue samples, which were markedly exacerbated by CYLD knockout. Moreover, mice with CYLD deficiency exhibited higher mortality rate induced by LPS treatment. In conclusion, these findings suggested that CYLD decrease might accelerate astrocyte activity by promoting pyroptosis to promote sepsis-associated brain injury, and CYLD might be a potential therapeutic target for the management of this disease.


Brain injury; CYLD; Caspase-1; LPS; Pyroptosis


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