Prevention of neuron and oligodendrocyte degeneration by interleukin-6 (IL-6) and IL-6 receptor/IL-6 fusion protein in organotypic hippocampal slices.
We investigated the effects of IL-6 and a chimeric derivative of IL-6 and soluble IL-6 receptor (IL6RIL6 chimera) on excitotoxic injury in rat organotypic hippocampal slices. Brief application of N-methyl-d-aspartate (NMDA) induced astrocyte reactivity, neuron cell death, and oligodendrocyte degeneration, the latter caused by secondary activation of AMPA/kainate receptors. Both these cytokines rescued neurons and oligodendrocytes, albeit the chimeric compound was much more potent and efficient than IL-6. No change was produced on reactive astrocytosis. The cytokines preserved myelin basic protein (MBP) production in slices exposed to excitotoxic insult, and when applied singularly for a week, they also enhanced both MBP and proteolipid protein expression. These effects occurred through activating the signal transducer gp130 and were associated with stimulation of transcription factors STAT1 and STAT3. Our results suggest that IL-6 and IL6RIL6 may prove to be valuable in treating neurodegenerative and demyelinating diseases.
Pizzi
Marina
M
Department of Biomedical Sciences and Biotechnologies, University of Brescia, 25123 Brescia, Italy. pizzi@med.unibs.it
Sarnico
Ilenia
I
Boroni
Flora
F
Benarese
Marina
M
Dreano
Michel
M
Garotta
Gianni
G
Valerio
Alessandra
A
Spano
PierFranco
P
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000503:physiopathology / Q000517:prevention & control; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000235:genetics; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494201:Il6st protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D016202:N-Methylaspartate