Regulation of NF-kappa B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations
Spilsbury A, Vauzour D, Spencer JPE, Rattray M
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 kappa B (NF-kappa 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-kappa B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF alpha, 150 ng/ml) increased NF-kappa B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I kappa B alpha construct. In addition, TNF alpha increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-kappa B 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 mu M) for 18 h. None of the flavonoids modulated constitutive or TNF alpha-induced NF-kappa B activity. Therefore, we conclude that NF-kappa B signalling in astrocytes is not a major target for flavonoids. (C) 2012 Elsevier Inc. All rights reserved.
Keywords:Inflammation;Astrocyte;Epicatechin;p65;TNF alpha;Flavonoids;Neurodegeneration