PMID- 18040799 OWN - NLM STAT- MEDLINE DCOM- 20071227 LR - 20220409 IS - 1557-1904 (Electronic) IS - 1557-1890 (Print) IS - 1557-1890 (Linking) VI - 1 IP - 3 DP - 2006 Sep TI - Up-regulation of BDNF in astrocytes by TNF-alpha: a case for the neuroprotective role of cytokine. PG - 212-22 AB - 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. FAU - Saha, Ramendra N AU - Saha RN AD - Section of Neuroscience, Department of Oral Biology, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE 68583-0740, USA. FAU - Liu, Xiaojuan AU - Liu X FAU - Pahan, Kalipada AU - Pahan K LA - eng GR - R01 NS039940/NS/NINDS NIH HHS/United States GR - NS48923/NS/NINDS NIH HHS/United States GR - NS39940/NS/NINDS NIH HHS/United States GR - R21 NS048923-01A2/NS/NINDS NIH HHS/United States GR - R01 NS039940-05A1/NS/NINDS NIH HHS/United States GR - R21 NS048923/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060516 PL - United States TA - J Neuroimmune Pharmacol JT - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JID - 101256586 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Cytokines/metabolism MH - Electrophoretic Mobility Shift Assay MH - Enzyme-Linked Immunosorbent Assay MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Gene Expression MH - Immunohistochemistry MH - NF-kappa B/metabolism MH - Neuroimmunomodulation/*physiology MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/*metabolism MH - Up-Regulation PMC - PMC2131740 MID - NIHMS26727 EDAT- 2007/11/28 09:00 MHDA- 2007/12/28 09:00 PMCR- 2007/12/11 CRDT- 2007/11/28 09:00 PHST- 2006/02/05 00:00 [received] PHST- 2006/04/19 00:00 [accepted] PHST- 2007/11/28 09:00 [pubmed] PHST- 2007/12/28 09:00 [medline] PHST- 2007/11/28 09:00 [entrez] PHST- 2007/12/11 00:00 [pmc-release] AID - 10.1007/s11481-006-9020-8 [doi] PST - ppublish SO - J Neuroimmune Pharmacol. 2006 Sep;1(3):212-22. doi: 10.1007/s11481-006-9020-8. Epub 2006 May 16.