title: Effects of resveratrol, piceatannol, tri-acetoxystilbene, and genistein on the inflammatory response of human peripheral blood leukocytes.
abstract: Inflammatory processes are involved in the etiology of diseases. We analyzed the effect of resveratrol, piceatannol, synthetic tri-acetoxystilbene (TAS), and genistein (Bonistein(TM)) on the production of inflammatory mediators including prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), interleukins, and chemokines, which participate in the progression of inflammation. In order to induce inflammatory responses, human peripheral blood mononuclear and/or polymorphonuclear leukocytes were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN(gamma)) and the production of PGE2, interleukin-8 (IL-8), and TNF-alpha was determined. In response to the stimuli, genes were substantially activated within < 2 h (e. g., TNF-alpha, IL-1alpha), or at a later stage, (e. g., COX-2, IL-6, IL-8). Unlike genistein, resveratrol and related compounds dose-dependently reduced PGE2 production. Genistein, piceatannol, and TAS diminished secretion of TNF-alpha, and IL-8. TAS reduced mRNA levels of COX-2, TNF-alpha, IL-8, IL-6, and IL-1alpha, while resveratrol impaired early expression of IL-8 and TNF-alpha. Piceatannol out-performed resveratrol, yet without matching TAS. Genistein downregulated TNF-alpha and IL-8 expression. These substances altered the LPS/IFNgamma-induced gene expression in mononuclear cells rather than in polymorphonuclear leukocytes. Immunoblot analyses corroborated the distinct activity pattern of resveratrol and genistein. In conclusion, resveratrol and their derivatives attenuated the inflammatory response of PBLs at several levels, whereas genistein acts on cytokines and pro-inflammatory interleukins.
authors.affiliation: DSM Nutritional Products, Kaiseraugst, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Richard
authors.forename: Debora
authors.initials: D
authors.lastname: Porath
authors.forename: Alexander
authors.initials: A
authors.lastname: Radspieler
authors.forename: Joseph
authors.initials: J
authors.lastname: Schwager
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; C041525:3,3',4,5'-tetrahydroxystilbene; D007371:Interferon-gamma; D019833:Genistein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077185:Resveratrol