Interleukin-6 protects cultured cerebellar granule neurons against glutamate-induced neurotoxicity.
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.
Peng
Yu-Ping
YP
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.
Qiu
Yi-Hua
YH
Lu
Jian-Hua
JH
Wang
Jian-Jun
JJ
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
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