Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations.
Spilsbury, A. Vauzour, D. Spencer, J.P.E. Rattray, Marcus
Spilsbury, A.
Vauzour, D.
Spencer, J.P.E.
Rattray, Marcus
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2012-02
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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.
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Spilsbury A, Vauzour D, Spencer JP and Rattray M (2012) Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations. Biochemical and Biophysical Research Communications, 418 (3): 578-583.
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