Up-regulation of BDNF in Astrocytes by TNF-α: A Case for the Neuroprotective Role of Cytokine

Abstract

Tumor necrosis factor-alpha (TNF-α) is widely known to be involved in physiological and pathophysiological processes of the brain where this proinflammatory cytokine is implicated with regulation of inflammatory and survival components. We report that TNF-α up-regulates exon-IVbdnf mRNA and brain-derived neurotrophic factor (BDNF) protein in primary astrocytes. The BDNF protein was detectable both in cellular lysate and in the extracellular medium. Activation of NF-κB by TNF-α and inhibition of TNF-α-induced BDNF expression by Δp65 (a dominant-negative mutant) and NEMO-binding domain peptide (an inhibitor of NF-κB) suggests that TNF-α induces BDNF expression through the activation of NF-κB. Similarly, TNF-α induced the activation of C/EBPβ and the expression of BDNF was sensitive to overexpression of ΔC/EBPβ (a dominant-negative mutant) and ETO (an inhibitor of C/EBPβ). Among three MAP kinases, TNF-α-induced BDNF up-regulation was sensitive only to inhibitors of ERK MAP kinase. However, the ERK MAP kinase pathway was coupled to activation of C/EBPβ but not NF-κB. Taken together, this study identifies a novel property of TNF-α in inducing the expression of BDNF via NF-κB and C/EBPβ in astrocytes that may be responsible for neurotrophic activity of the cytokine.

Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis

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Activation of Peroxisome Proliferator-activated Receptor α Induces Lysosomal Biogenesis in Brain Cells

“…Immunoblotting-Western blotting was conducted as described earlier (23,32) with modifications. Briefly, cells were scraped in 1ϫ RIPA buffer; protein was measured using Bradford reagent, and SDS buffer was added and electrophoresed on NuPAGE Novex 4 -12% BisTris gels (Life Technologies, Inc.); and proteins were transferred onto a nitrocellulose membrane (Bio-Rad) using the ThermoPierce Fast Semi-Dry Blotter.…”

Chorioamnionitis: a multiorgan disease of the fetus?

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