title: cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages.
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.
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Laboratory of Nanomaterials, Chang Gung University, Taoyuan, Taiwan, Republic of China Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Tsung-Teng
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China hclai@mail.cgu.edu.tw.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Institute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Young-Bin
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan, Republic of China.
authors.forename: Lih-Geeng
authors.initials: LG
authors.lastname: Chen
authors.affiliation: Cancer Research Center, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei, Taiwan, Republic of China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Ko
authors.affiliation: Department of Respiratory Therapy, Fu Jen Catholic University, Taipei, Taiwan, Republic of China.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Laboratory of Nanomaterials, Chang Gung University, Taoyuan, Taiwan, Republic of China Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Cheng-Yeu
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Laboratory of Nanomaterials, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Jan
authors.initials: J
authors.lastname: Martel
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Molecular Cell Biology, Health Sciences Research Institute, University of California Merced, Merced, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Kowit-Yu
authors.initials: KY
authors.lastname: Chong
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Laboratory of Nanomaterials, Chang Gung University, Taoyuan, Taiwan, Republic of China Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei, Taiwan, Republic of China Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Young
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D058847:Inflammasomes; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000077185:Resveratrol
keywords: Resveratrol; caspase; inflammasome; interleukin-1β; reactive oxygen species