Publications
Detailed Information
Suppression of Syk activation by resveratrol inhibits MSU crystal-induced inflammation in human monocytes
Cited 15 time in
Web of Science
Cited 17 time in Scopus
- Authors
- Issue Date
- 2019-03
- Publisher
- Springer Verlag
- Citation
- Journal of Molecular Medicine, Vol.97 No.3, pp.369-383
- Abstract
- Monosodium urate (MSU) crystals are an endogenous sterile particulate that has been identified as a potent damage-associated molecular pattern (DAMP). In humans, the induction of IL-1 production through MSU-induced NLRP3 inflammasome activation in monocytes/macrophages is responsible for pathogenesis of gouty arthritis. It was recently reported that in a murine model of this disease, resveratrol decreases MSU-induced recurrent attacks of gouty arthritis. Despite its demonstrated anti-inflammatory effects, the mechanisms underlying resveratrol-mediated repression of IL-1 production in MSU-activated monocytes remain poorly understood. Here, we show that resveratrol suppresses secretion of active IL-1 by human primary monocytes stimulated with MSU crystals through suppression of Syk activation. Metabolic labeling and pull-down assays to investigate de novo protein synthesis clearly demonstrated that intracellular pro-IL-1 synthesis is rapidly repressed in monocytes after resveratrol treatment due to decreased phosphorylation of Syk and p38. Resveratrol also inhibited NLRP3 inflammasome activation in MSU-stimulated monocytes by suppressing oligomerization of ASC. Furthermore, resveratrol exerted a beneficial effect by reducing IL-1 production and inhibiting neutrophil recruitment in a mouse model of MSU-mediated peritonitis. Our findings suggest that resveratrol exerts anti-inflammatory effects via post-translational regulation of IL-1 production and, thus, may prove beneficial for the treatment of MSU crystal-mediated sterile inflammation.Key messageResveratrol has negative effects on pro-IL-1 synthesis through Syk and p38.Resveratrol inhibits oligomerization of ASC.Resveratrol is beneficial in a mouse model of MSU-induced peritonitis.
- ISSN
- 0946-2716
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.