| Up-regulation of BDNF in astrocytes by TNF-alpha: a case for the neuroprotective role of cytokine. | |
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MedLine Citation:
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PMID: 18040799 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tumor necrosis factor-alpha (TNF-alpha) 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-alpha up-regulates exon-IV-bdnf 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-kappaB by TNF-alpha and inhibition of TNF-alpha-induced BDNF expression by Deltap65 (a dominant-negative mutant) and NEMO-binding domain peptide (an inhibitor of NF-kappaB) suggests that TNF-alpha induces BDNF expression through the activation of NF-kappaB. Similarly, TNF-alpha induced the activation of C/EBPbeta and the expression of BDNF was sensitive to overexpression of DeltaC/EBPbeta (a dominant-negative mutant) and ETO (an inhibitor of C/EBPbeta). Among three MAP kinases, TNF-alpha-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/EBPbeta but not NF-kappaB. Taken together, this study identifies a novel property of TNF-alpha in inducing the expression of BDNF via NF-kappaB and C/EBPbeta in astrocytes that may be responsible for neurotrophic activity of the cytokine. |
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Authors:
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Ramendra N Saha; Xiaojuan Liu; Kalipada Pahan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-05-16 |
Journal Detail:
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Title: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology Volume: 1 ISSN: 1557-1904 ISO Abbreviation: J Neuroimmune Pharmacol Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2007-11-27 Completed Date: 2007-12-27 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 101256586 Medline TA: J Neuroimmune Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 212-22 Citation Subset: IM |
Affiliation:
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Section of Neuroscience, Department of Oral Biology, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE 68583-0740, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / metabolism* Blotting, Western Brain-Derived Neurotrophic Factor / metabolism* Cells, Cultured Cytokines / metabolism Electrophoretic Mobility Shift Assay Enzyme-Linked Immunosorbent Assay Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Immunohistochemistry NF-kappa B / metabolism Neuroimmunomodulation / physiology* Rats Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha / metabolism* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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NS39940/NS/NINDS NIH HHS; NS48923/NS/NINDS NIH HHS; R01 NS039940-05A1/NS/NINDS NIH HHS; R21 NS048923-01A2/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Brain-Derived Neurotrophic Factor; 0/Cytokines; 0/NF-kappa B; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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