TXNIP-mediated nuclear factor-κB signaling pathway and intracellular shifting of TXNIP in uric acid-induced NLRP3 inflammasome

• Published in: Biochemical and biophysical research communications 2019-04, Vol.511 (4), p.725-731
• Main Authors: Kim, Seong-Kyu, Choe, Jung-Yoon, Park, Ki-Yeon
• Format: Article
• Language: English
• Subjects: Carrier Proteins - immunology; Humans; Inflammasomes - immunology; Inflammation - immunology; Macrophages - immunology; Monosodium urate; NF-kappa B - immunology; NF-κB; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLRP3; Reactive oxygen species; Reactive Oxygen Species - immunology; Signal Transduction; TXNIP; Uric Acid - immunology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.02.141

The aim of this study was to assess the role of thioredoxin-interacting protein (TXNIP) in nuclear factor-κB (NF-κB) signaling and the interaction between TXNIP and NOD-like receptor protein 3 (NLRP3) in activation of the NLRP3 inflammasome in monosodium urate (MSU)-induced inflammation. Interleukin-1β (IL-1β), IL-18, caspase-1, phospho-IκBα (pIκBα), phospho-NF-κB, (pNF-κB), and TXNIP in U937 macrophage-like cells treated with MSU crystals were analyzed using western blotting and real-time polymerase chain reaction (RT-PCR). Expression of these molecules was also assessed in U937 macrophages transfected with TXNIP siRNA and treated with antioxidants. U937 macrophages treated with MSU crystals showed increased expression of IL-1β, IL-18, caspase-1, and TXNIP and activation of NF-κB signaling, which were strongly inhibited by addition of antioxidants or transfection with TXNIP siRNA. Intracellular translocation of TXNIP from the nucleus to mitochondria was observed in cells treated with MSU crystals. And quercetin and ascorbic acid suppressed translocation of TXNIP. Binding between TXNIP and NLRP3 under oxidative stress caused by MSU crystals was observed and was blocked by quercetin or ascorbic acid. This study showed that activation of MSU-induced NLRP3 inflammasome requires TXNIP-mediated NF-κB signaling pathway and intracellular TXNIP shifting. •IL-1β, IL-18 and NF-κB signaling were inhibited by transfection with TXNIP siRNA.•Intracellular TXNIP shifting from the nucleus to mitochondria was observed in cells treated with MSU crystals.•Interaction of TXNIP with NF-κB signaling is a crucial in uric acid-induced inflammation.