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Inhibition of CCAAT/enhancer binding protein δ expression by chrysin in microglial cells results in anti‐inflammatory and neuroprotective effects
Author(s) -
GresaArribas Núria,
Serratosa Joan,
Saura Josep,
Solà Carme
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06952.x
Subject(s) - neuroinflammation , chrysin , neuroprotection , microglia , ccaat enhancer binding proteins , nitric oxide synthase , microbiology and biotechnology , chemistry , nitric oxide , biology , pharmacology , transcription factor , inflammation , biochemistry , immunology , endocrinology , nuclear protein , antioxidant , flavonoid , gene
J. Neurochem. (2010) 115 , 526–536. Abstract The control of neuroinflammation is a potential target to be considered in the treatment of neurodegenerative diseases. It is therefore important to find anti‐inflammatory drugs and study new targets that inhibit neuroinflammation. We designed an experimental model of neuroinflammation in vitro to study the anti‐inflammatory and neuroprotective effects of the flavonoid chrysin and the involvement of nuclear factor‐κB p65 and CCAAT/enhancer binding proteins (C/EBPs) β and δ transcription factors in its mechanism of action. We used primary cultures of mouse embryonic cortical neurons and cultures of BV2 (murine microglial cell line) or mouse primary microglia. We induced neuronal death in neuronal‐BV2/microglial co‐cultures using lipopolysaccharide of Escherichia coli and interferon‐γ. Chrysin pre‐treatment inhibited nitric oxide and tumor necrosis factor‐α production, as well as inducible nitric oxide synthase expression in lipopolysaccharide E. coli and interferon‐γ‐treated microglial cells, but did not affect cyclooxygenase‐2 expression. Chrysin pre‐treatment also protected neurons against the neurotoxicity induced by reactive microglial cells. These effects were associated to a decrease in C/EBPδ protein level, mRNA expression, and DNA‐binding activity, with no effect on C/EBPβ and p65 nuclear protein levels or DNA‐binding activity, pointing out C/EBPδ as a possible mediator of chrysin effects. Consequently, C/EBPδ is a possible target to act against neuroinflammation in neurodegenerative processes.