Spilsbury, A, Vauzour, D ORCID: https://orcid.org/0000-0001-5952-8756, Spencer, JPE and Rattray, M (2011) Regulation of NF-kappaB activity in astrocytes: the effects of flavonoids at dietary-relevant concentrations. In: 10th European Meeting on Glial Cells in Health and Disease, 2011-09-13 - 2011-09-17.
Full text not available from this repository. (Request a copy)Abstract
Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Sustained activation of nuclear transcription factor kappa B (NF-kB) is thought toplay an important role in the pathogenesis of neurodegenerative disorders. Activation of the NF-kB pathway in astrocytes may elicit a pro-inflammatory response through increased production and secretion of cytokines such as IL-1, IL-6, TNFa and IFN-g and of nitric oxide. Through secretion of these molecules, astrocytes may injure surrounding neurons. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties both in vivo and in vitro, mainly through their capacity to modulate a number of intracellular signaling pathways. In this study we investigated whether different classes of flavonoids were able to modulate NF-kB signaling in embryonic mouse cortical astrocytes. Using luciferase reporter assays, we found that NF-kB-mediated transcription was increased by addition of TNFa (150 ng / mL), and this increase was abolished on cotransfection of a dominant-negative IkB-alpha construct. In addition, TNFalpha induced rapid phosphorylation of IkB-alpha as determined by Western blotting, and increased nuclear localization of p65 as shown by immunocytochemistry and live cell imaging of a GFP-tagged construct. To investigate potential flavonoid modulation of NF-kB activity, astrocytes were treated with flavonoids from different classes; Flavan-3-ols ((-)-epicatechin and (+)-catechin hydrate), flavones (luteolin and chrysin), flavonol (kaempferol) or flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1–1 µM) for 18 h. None of the flavonoids modulated constitutive or TNFa induced NF-kB activity. Therefore, we conclude that NF-kB signaling in astrocytes is not a major target for flavonoids at these concentrations.
Item Type: | Conference or Workshop Item (Other) |
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Uncontrolled Keywords: | nf-kappab,neuroprotection,flavonoids |
Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
Depositing User: | David Vauzour |
Date Deposited: | 29 Feb 2012 11:15 |
Last Modified: | 06 Jun 2024 14:30 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/34951 |
DOI: |
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