cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages.

Tsung-Teng Huang, Hsin-Chih Lai, Young-Bin Chen, Lih-Geeng Chen, Yi-Hui Wu, Yun-Fei Ko, Chia-Chen Lu, Chih-Jung Chang, Cheng-Yeu Wu, Jan Martel, David M Ojcius, Kowit-Yu Chong, John D Young

Index: Innate Immunity 20(7) , 735-50, (2014)

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Abstract

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-1β by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1β production and IL-1β 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 E2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein. These results indicate that cis-resveratrol produces anti-inflammatory effects by inhibiting both the canonical and non-canonical inflammasomes, and associated pathways in human macrophages.© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.