title: Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations.
abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.
authors.affiliation: Reading School of Pharmacy, University of Reading, Reading RG6 6UB, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Spilsbury
authors.forename: David
authors.initials: D
authors.lastname: Vauzour
authors.forename: Jeremy P E
authors.initials: JP
authors.lastname: Spencer
authors.forename: Marcus
authors.initials: M
authors.lastname: Rattray
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002392:Catechin / Q000494:pharmacology; D002478:Cells, Cultured; D004032:Diet; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D016328:NF-kappa B; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin