Suppression of Syk activation by resveratrol inhibits MSU crystal-induced inflammation in human monocytes

Yeon Ho Chung, Hee Young Kim, Bo Ruem Yoon, Yeon Jun Kang, Won Woo Lee

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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-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.

Original languageEnglish
Pages (from-to)369-383
Number of pages15
JournalJournal of Molecular Medicine
Volume97
Issue number3
DOIs
StatePublished - 7 Mar 2019

Bibliographical note

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • Gouty arthritis
  • IL-1β
  • MSU
  • NLRP3 inflammasome
  • Resveratrol
  • Syk

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