Effects of IL-6 secreted from astrocytes on the survival of dopaminergic neurons in lipopolysaccharide-induced inflammation.
The role of astrocytes in microglia-induced neuronal death remains controversial. In this study, astrocytes and astrocyte-derived conditioned media (ACM) supported the survival of dopaminergic neurons, and the former was more effective than the latter. In the presence of astrocytes, low concentrations of LPS enhanced the survival of dopaminergic neurons, while high concentrations attenuated survival. LPS dramatically induced astrocytes to secrete IL-6 in a dose-dependent manner with no effect on secretion of GDNF. Neuron-astrocyte cultures had highest secretion of GDNF, followed by ACM-treated neuron-enriched cultures. After neuron-astrocyte cultures treated with IL-6-neutralizing antibody, both effects of the enhanced and attenuated survival of dopaminergic neurons were abolished. Our results indicate that astrocytes play a protective role in the LPS-induced damage of dopaminergic neurons in certain circumstances, and the interaction between astrocytes and dopaminergic neurons may enhance the protective effect of astrocytes. Suitable activation of astrocytes increases the protective effect while excessive activation attenuates it, and IL-6 might mediate this dual action. The underlying mechanisms related to the secretion of GDNF and proinflammatory factors warrant further investigation.
Li
Xue-zhong
XZ
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Bai
Long-mei
LM
Yang
Ya-ping
YP
Luo
Wei-feng
WF
Hu
Wei-dong
WD
Chen
Ju-ping
JP
Mao
Cheng-jie
CJ
Liu
Chun-feng
CF
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D019610:Cytoprotection / Q000276:immunology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D010300:Parkinson Disease / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology
D051100:Glial Cell Line-Derived Neurotrophic Factor; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D004298:Dopamine