title: Neuroprotection of Neuro2a cells and the cytokine suppressive and anti-inflammatory mode of action of resveratrol in activated RAW264.7 macrophages and C8-B4 microglia.
abstract: Chronic inflammation is a hallmark of neurodegenerative disease and cytotoxic levels of nitric oxide (NO) and pro-inflammatory cytokines can initiate neuronal death pathways. A range of cellular assays were used to assess the anti-inflammatory and neuroprotective action of resveratrol using murine microglial (C8-B4), macrophage (RAW264.7) and neuronal-like (Neuro2a) cell lines. We examined the release of NO by Griess assay and used a Bioplex array to measure a panel of pro- and anti-inflammatory cytokines and chemokines, in response to the inflammatory stimuli lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Resveratrol was a potent inhibitor of NO and cytokine release in activated macrophages and microglia. The activity of resveratrol increased marginally in potency with longer pre-incubation times in cell culture that was not due to cytotoxicity. Using an NO donor we show that resveratrol can protect Neuro2a cells from cytotoxic concentrations of NO. The protective effect of resveratrol from pro-inflammatory signalling in RAW264.7 cells was confirmed in co-culture experiments leading to increased survival of Neuro2a cells. Together our data are indicative of the potential neuroprotective effect of resveratrol during nitrosative stress and neuroinflammation.
authors.affiliation: Dept of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Steiner
authors.affiliation: Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Balez
authors.affiliation: Dept of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, Australia.
authors.forename: Niloo
authors.initials: N
authors.lastname: Karunaweera
authors.affiliation: School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW, Australia.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
authors.affiliation: Dept of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, Australia; National Institute of Complementary Medicine (NICM), Western Sydney University, Australia; Molecular Medicine Research Group, University of Western Sydney, Australia.
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
authors.affiliation: Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia. Electronic address: lezanne@uow.edu.au.
authors.forename: Lezanne
authors.initials: L
authors.lastname: Ooi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects* / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D013267:Stilbenes; D000077185:Resveratrol
keywords: Anti-inflammatory; Neuroprotection; Nitric oxide; Resveratrol