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 kappa B (NF-kB) is thought toplay an important role in the pathogenesis of neurodegenerative disorders. Activation of the NF-kB pathway in astrocytes may elicit a pro-inflammatory response through increased production and secretion of cytokines such as IL-1, IL-6, TNFa and IFN-g and of nitric oxide. Through secretion of these molecules, astrocytes may injure surrounding neurons. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties both in vivo and in vitro, mainly through their capacity to modulate a number of intracellular signaling pathways. In this study we investigated whether different classes of flavonoids were able to modulate NF-kB signaling in embryonic mouse cortical astrocytes. Using luciferase reporter assays, we found that NF-kB-mediated transcription was increased by addition of TNFa (150 ng / mL), and this increase was abolished on cotransfection of a dominant-negative IkB-alpha construct. In addition, TNFalpha induced rapid phosphorylation of IkB-alpha as determined by Western blotting, and increased nuclear localization of p65 as shown by immunocytochemistry and live cell imaging of a GFP-tagged construct. To investigate potential flavonoid modulation of NF-kB activity, astrocytes were treated with flavonoids from different classes; Flavan-3-ols ((-)-epicatechin and (+)-catechin hydrate), flavones (luteolin and chrysin), flavonol (kaempferol) or 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-kB activity. Therefore, we conclude that NF-kB signaling in astrocytes is not a major target for flavonoids at these concentrations.
|Publication status||Published - Oct 2011|
|Event||10th European Meeting on Glial Cells in Health and Disease - Prague|
Duration: 13 Sep 2011 → 17 Sep 2011
|Conference||10th European Meeting on Glial Cells in Health and Disease|
|Period||13/09/11 → 17/09/11|