Regulation of NF-κB activity in astrocytes: Effects of flavonoids at dietary-relevant concentrations

Spilsbury, Alison, Vauzour, David, Spencer, Jeremy P. E. and Rattray, Marcus (2012) Regulation of NF-κB activity in astrocytes: Effects of flavonoids at dietary-relevant concentrations. Biochemical and Biophysical Research Communications, 418 (3). 578–583. ISSN 1090-2104

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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 ?B (NF-?B) 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-?B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFa, 150 ng/ml) increased NF-?B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I?Ba construct. In addition, TNFa increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-?B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin hydrate), 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 TNFa-induced NF-?B activity. Therefore, we conclude that NF-?B signalling in astrocytes is not a major target for flavonoids.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: David Vauzour
Date Deposited: 13 Feb 2012 12:46
Last Modified: 21 Apr 2020 16:28
URI: https://ueaeprints.uea.ac.uk/id/eprint/36725
DOI: 10.1016/j.bbrc.2012.01.081

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