Recombinant Yeast Thioredoxin 1

Emerging evidence suggests that NLRP3 inflammasome was associated with various kinds of immunological diseases including colitis. However, there are few drugs targeting inflammasomes in the treatment of colitis. Several flavonoids have been found to affect the inflammasome pathway, but the mechanism is still confusing. Here we report that VI-16, a synthetic flavonoid compound, exerts potent anti-inflammatory effects on macrophages in DSS-induced colitis mice, which intervened in the activation of NLRP3 inflammasome without affecting intestinal epithelial cells. However, the protection of VI-16 against DSS-induced colitis was dependent on NLRP3 expression in hematopoietic cells. Furthermore, this inhibitory effect of VI-16 was found to be at least partially achieved by decreasing the mitochondria) ROS generation without affecting autophagy. Further studies confirm that VI-16 inhibits the binding of Txnip to NLRP3 by reducing oxidative stress and ultimately inhibits NLRP3 inflammasome. This demonstrates the ability of VI-16 to inhibit the NLRP3 inflammasome activation and its potential use in the treatment of inflammatory bowel disease.

Previous studies have shown that chronic stress and chronic stress hormone treatment induce oxidative damage in rodents. Thioredoxin (Trx) is a small redox protein that plays an important role in regulation of oxidative protein cysteine modification. A Trx reduced state is maintained by thioredoxin reductase (TrxR), and the thioredoxin-interacting protein (Txnip) is an endogenous inhibitor of Trx. The purpose of this study was to investigate the effects of chronic treatment with stress hormone corticosterone on Trx, TrxR and Txnip in cultured neuronal cells. Using immunoblotting analysis we found that although chronic corticosterone treatment had no effect on Trx and TrxR protein levels, this treatment significantly increased Txnip protein levels. Using immunocytochemistry we also found that chronic corticosterone treatment increased Txnip in both nucleus and cytosol, while glucocorticoid receptor inhibitor RU486 can block corticosterone-increased Txnip protein levels. Using biotin switch, dimedone conjugation and CRISPR/Cas9 methods we found that chronic corticosterone treatment increased protein nitrosylation and sulfenylation, while knocking out Txnip blocked corticosterone-induced protein nitrosylation and sulfenylation. Since Trx can reduce cysteine oxidative protein modification such as nitrosylation and sulfenylation, our findings suggest that chronic corticosterone treatment may upregulate Txnip by targeting glucocorticoid receptor, subsequently inhibiting Trx activity and enhancing oxidative protein cysteine modification, which contributes to corticosterone-caused oxidative damage. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.