title: Interleukin-6 protects cultured cerebellar granule neurons against glutamate-induced neurotoxicity.
abstract: Cytokine interleukin-6 (IL-6) has been showed to be an important mediator of neuroimmune responses. However, effects of IL-6 in the central nervous system (CNS) are quite complex and diverse, and mechanisms through which IL-6 influences neuronal functions are primarily unknown. In the present study, we explored protective effect of IL-6 that was chronically applied to cerebellar granule neurons (CGNs) in culture against neurodamage induced by glutamate and mechanisms involved in the neuroprotective effect of IL-6. The chronic IL-6 exposure significantly prevented the CGNs from the glutamate-induced attenuation of neuronal vitality. This neuroprotective effect of IL-6 depended on its concentrations. IL-6 at 2.5 ng/ml did not markedly improve the neuronal vitality, but IL-6 at 5 and 10 ng/ml notably improved the neuronal vitality. The glutamate-evoked neuronal apoptosis also was strikingly inhibited by the chronic IL-6 pretreatment. Intracellular Ca2+ in the CGNs lacking IL-6 pretreatment acutely rose as soon as these neurons were stimulated by glutamate and were maintained at higher levels during the whole 18-min period of glutamate attack. Although intracellular Ca2+ in the IL-6-pretreated CGNs also produced an acute and transient elevation in response to the glutamate insult, they quickly dropped and recovered to basal levels before the glutamate application. Anti-gp130 monoclonal antibody (mAb) blocked the suppressive effect of IL-6 on the glutamate-induced intracellular Ca2+ overload. These results reveal that IL-6 can protect neurons against glutamate-induced neurotoxicity, and suggest that the neuroprotective effect of IL-6 may be via gp130 signal transducing pathway to suppress the glutamate-evoked intracellular Ca2+ overload.
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Mailbox 426, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D050822:Cytokine Receptor gp130; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018698:Glutamic Acid / Q000633:toxicity*; D020287:In Situ Nick-End Labeling / Q000379:methods; D015850:Interleukin-6 / Q000008:administration & dosage*; D008562:Membrane Glycoproteins / Q000276:immunology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494201:Il6st protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130; D018698:Glutamic Acid; D002118:Calcium