cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages (original) (raw)

Resveratrol, a natural phenolic compound found in red grapes and wine, exists as cis and trans isomers. Recent studies have shown that trans-resveratrol possesses anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-tumor and immunomodulatory properties. However, it remains unclear whether cis-resveratrol may exhibit similar activities. The objective of the present study was to examine the effects of cis-and trans-resveratrol on the production of pro-inflammatory cytokines and mediators in human macrophages. We examined the possibility that cis-and trans-resveratrol may affect cytokine secretion by modulating inflammasomes, intracellular multi-protein complexes, the assembly of which leads to caspase-1 activation and secretion of active IL-1b by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1b production and IL-1b secretion, but also suppresses ATP-induced transcription and activation of caspase-1 and caspase-4. Notably, cis-resveratrol inhibits the expression of the purinergic receptor, P2X 7 R, and the endoplasmic reticulum stress marker, Glc-regulated protein 78, but also reduces reactive oxygen species production. Moreover, cis-resveratrol attenuates cyclooxygenase-2 expression and prostaglandin E 2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein.

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