A mechanistic insight into curcumin modulation of the IL-1β secretion and NLRP3 S-glutathionylation induced by needle-like cationic cellulose nanocrystals in myeloid cells. (25th August 2017)

• Record Type: Journal Article
• Authors: Guglielmo, Andrew; Sabra, Adham; Elbery, Mostafa; Cerveira, Milena M.; Ghenov, Fernanda; Sunasee, Rajesh; Ckless, Karina
• Is Part Of: Chemico-biological interactions. Volume 274(2017)
• Page Start: 1
• Page End: 12
• Publication Date: 2017-08-25
• Subjects: Curcumin -- NLRP3 inflammasome -- IL-1β -- S-glutathionylation -- Nanomaterials -- Cellulose nanocrystals; AP-1 activator protein-1 -- ASC apoptosis-associated speck-like protein containing a CARD -- CNC-AEMA2 cellulose nanocrystals-grafted-poly(N-aminoethylmethacrylamide) -- DAMPS danger-associated molecular pattern molecules -- DLS dynamic light scattering -- DTT dithiothreitol -- ELISA enzyme-linked immuno assay -- eNOS endothelial nitric oxide synthase -- GST glutathione-S-transferase -- HO-1 heme oxygenase-1 -- HRP horseradish peroxidase-conjugated -- IL-1β Interleukin 1β -- CNCs cellulose nanocrystals -- KC keratinocyte chemoattractant -- LPS lipopolysaccharide -- LSM Lymphocyte separation medium -- MD-2 myeloid differentiation protein 2 -- MIP-2 macrophage inflammatory protein 2 -- MPB 3-(N-Maleimidopropionyl)-biocytin -- NF-κB nuclear factor kappa B -- NLRP3 NOD-like receptor, pyrin domain-containing 3 -- Nrf2 nuclear factor (erythroid derived 2)-like 2 -- oxPTM oxidative post-translational modifications -- PAMPs pathogen-associated molecular pattern molecules -- PBMCs peripheral blood mononuclear cells -- PSSG protein S-glutathionylation -- ROS reactive oxygen species -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel -- TRL toll-like receptor -- Trx2 thioredoxin 2 -- γ-GCL γ-glutamyl cysteine ligase; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.06.028
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Recently we have demonstrated that needle-like cationic cellulose nanocrystals (CNC-AEMA2) evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway. In this study we demonstrated that curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa (Zingiberaceae), was able to suppress, at least in part, this immunological response, as observed by diminished IL-1β secretion in CNC-AEMA2-stimulated macrophages primed with LPS. Curcumin is a well-known antioxidant and anti-inflammatory natural compound and in addition to acting as "scavenger" of reactive oxygen species (ROS), it can also upregulates antioxidant enzymes. However, the mechanisms by which this natural compound exerts its protective activity is still under investigation. We hypothesize that curcumin may also affect S-glutathionylation of key proteins involved in the NLRP3 inflammasome/IL-1β pathway, and therefore impact their protein-protein interactions. The goal of this study was to investigate the effects of curcumin on the S-glutathionylation of NLRP3 induced by CNC-AEMA2 in LPS-primed mouse macrophages (J774A.1), as well as interactions among proteins of the NLRP3 inflammasome complex. Our main finding indicates that the addition of curcumin concomitantly with LPS caused the greatest decrease in NLRP3 S-glutathionylation and a respective increase in caspase-1 S-glutathionylation, which appears to favor protein-protein interactions in the NLRP3 complex. Taking together, our results suggest that, at least in part, the anti-inflammatory activity of curcumin is associated with changes in S-glutathionylation of key NLRP3 inflammasome components, and perhaps resulting in sustained complex assembly and suppression of IL-1β secretion. Highlights: Curcumin suppressed IL-1β secretion induced by cellulose nanocrystals. Cellulose nanocrystals induced S-glutathionylation of the NLRP3 protein. Curcumin attenuated S-glutathionylation of the NLRP3 protein.