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

Alison Spilsbury, David Vauzour, Jeremy P. E. Spencer, Marcus Rattray

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)578–583
JournalBiochemical and Biophysical Research Communications
Volume418
Issue number3
DOIs
Publication statusPublished - 17 Feb 2012

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