Suppression of Syk activation by resveratrol inhibits MSU crystal-induced inflammation in human monocytes
| Autor: | Bo Ruem Yoon, Yeon Jun Kang, Hee Young Kim, Yeon-Ho Chung, Won Woo Lee |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
p38 mitogen-activated protein kinases
Syk Inflammation Peritonitis Resveratrol p38 Mitogen-Activated Protein Kinases Monocytes Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Animals Humans Syk Kinase Secretion Cells Cultured Genetics (clinical) Chemistry Uric Acid Cell biology Mice Inbred C57BL Cytokines Molecular Medicine Phosphorylation Female medicine.symptom Intracellular 030215 immunology |
| Zdroj: | Journal of Molecular Medicine. 97:369-383 |
| ISSN: | 1432-1440 0946-2716 |
| Popis: | 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-1β 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-1β production in MSU-activated monocytes remain poorly understood. Here, we show that resveratrol suppresses secretion of active IL-1β 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-1β 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-1β 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-1β production and, thus, may prove beneficial for the treatment of MSU crystal-mediated sterile inflammation. KEY MESSAGE: Resveratrol has negative effects on pro-IL-1β synthesis through Syk and p38. Resveratrol inhibits oligomerization of ASC. Resveratrol is beneficial in a mouse model of MSU-induced peritonitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink