title: The effect of gp130 stimulation on glutamate-induced excitotoxicity in primary hippocampal neurons.
abstract: Primary hippocampal neurons from newborn rats treated with glutamate showed clear excitotoxicity. This excitotoxicity could be reversed by treatment of the cells with cytokines of the interleukin-6 family. Stimulation of gp130 on hippocampal neurons resulted in tyrosine phosphorylation of STAT3 and activation of p42 and p44 MAP kinases. Receptors for the interleukin-6 type cytokines are active in membrane bound and soluble form. To address the question whether the neurotrophic effect of interleukin-6 type cytokines requires soluble cytokine receptors we used fusion proteins of interleukin-6 coupled to the soluble interleukin-6 receptor and ciliary neurotrophic factor coupled to the soluble ciliary neurotrophic factor receptor. Ciliary neurotrophic factor was as active as the cytokine-receptor fusion protein, indicating that hippocampal neurons express ciliary neurotrophic factor receptor on the cell surface. In contrast, interleukin-6 was only active at very high concentrations whereas the fusion protein of interleukin-6 coupled to the soluble interleukin-6 receptor (Hyper-IL-6) exhibited high neurotrophic activity at the same concentrations as ciliary neurotrophic factor. These data indicate that interleukin-6 receptor expression is very low on hippocampal neurons and that gp130 stimulation can be used to rescue hippocampal neurons from excitotoxicity.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Pia
authors.initials: P
authors.lastname: März
authors.forename: Uwe
authors.initials: U
authors.lastname: Otten
authors.forename: Jiguang
authors.initials: J
authors.lastname: Ge
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology*; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D006224:Cricetinae; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D018698:Glutamic Acid; D020928:Mitogen-Activated Protein Kinases