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Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation by Jianjun Jiang; Yining Shi; Jiyu Cao; Youjin Lu; Gengyun Sun; Jin Yang is a scholarly article available to read on EtoBox.

What is Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation about?

## Abstract Background: This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms.Methods: Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content.Results: Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addi

Author

Jianjun Jiang; Yining Shi; Jiyu Cao; Youjin Lu; Gengyun Sun; Jin Yang

Publisher

Research Square Platform LLC

Published

2021

Language

EN