Soluble interleukin-6 (IL-6) receptor/IL-6 fusion protein enhances in vitro differentiation of purified rat oligodendroglial lineage cells

Alessandra Valerio, Marina Ferrario, Michel Dreano, Gianni Garotta, Pierfranco Spano, Marina Pizzi

Research output: Contribution to journalArticle

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Abstract

We investigated the effects of a chimeric protein (IL6RIL6 chimera) containing interleukin-6 (IL-6) fused to its soluble receptor (sIL-6R) on the proliferation and/or differentiation of rat oligodendrocyte progenitor cells (OPCs) and on oligodendrocyte survival. Exposure of OPCs to IL6RIL6 chimera for 48 h induced a dose-dependent decrease of bromodeoxyuridine (BrdU) incorporation. IL6RIL6 chimera treatment for 48 h also strongly increased the reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium (MTS) by mitochondrial enzymes and enhanced oligodendrocyte staining with a mitochondrial fluorescent dye. A strong, dose-dependent increase in the number and length of processes immunostained for early (galactocerebroside) or late (myelin basic protein) oligodendrocyte differentiation markers was revealed after OPC treatment with IL6RIL6 chimera for 2-7 days, respectively. Moreover, treatment with IL6RIL6 chimera improved oligodendrocyte survival. The chimera-induced increase of oligodendrocyte arborization was mimicked, although with lower efficacy, by ciliary neurotrophic factor (CNTF) but not by IL-6 and was reduced in the presence of a gp130 soluble peptide which is able to inhibit the gp130-mediated signals of the IL-6/sIL-6R complex. Oligodendrocyte treatment with IL6RIL6 chimera for 30 min induced both signal transducer and the activator of transcription-1 (STAT-1) and STAT-3 phosphorylation and nuclear translocation. We conclude that, by interacting with membrane gp130 and possibly by activating Janus kinase/STAT pathways, IL6RIL6 chimera induces OPCs to differentiate into mature oligodendrocytes, promotes their survival, and could deserve investigation as a therapeutic strategy for enhancing remyelination.

Original languageEnglish
Pages (from-to)602-615
Number of pages14
JournalMolecular and Cellular Neuroscience
Volume21
Issue number4
DOIs
Publication statusPublished - 2002

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Oligodendroglia
Stem Cells
Interleukin-6
In Vitro Techniques
interleukin 6-interleukin 6 receptor fusion protein, recombinant
Cytokine Receptor gp130
Tetrazolium Salts
STAT1 Transcription Factor
Ciliary Neurotrophic Factor
Janus Kinases
Myelin Basic Protein
Differentiation Antigens
Bromodeoxyuridine
Fluorescent Dyes
Phosphorylation
Staining and Labeling
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Soluble interleukin-6 (IL-6) receptor/IL-6 fusion protein enhances in vitro differentiation of purified rat oligodendroglial lineage cells. / Valerio, Alessandra; Ferrario, Marina; Dreano, Michel; Garotta, Gianni; Spano, Pierfranco; Pizzi, Marina.

In: Molecular and Cellular Neuroscience, Vol. 21, No. 4, 2002, p. 602-615.

Research output: Contribution to journalArticle

Valerio, Alessandra ; Ferrario, Marina ; Dreano, Michel ; Garotta, Gianni ; Spano, Pierfranco ; Pizzi, Marina. / Soluble interleukin-6 (IL-6) receptor/IL-6 fusion protein enhances in vitro differentiation of purified rat oligodendroglial lineage cells. In: Molecular and Cellular Neuroscience. 2002 ; Vol. 21, No. 4. pp. 602-615.
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