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PMID: 8676083 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Accelerated Nerve Regeneration in Mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma.

The Journal of experimental medicine ·Vol. 183 ·No. 6 ·1996-06-01 ·Pages 2627-34

Hirota H, Kiyama H, Kishimoto T, Taga T

Abstract

In this study we aimed to examine a role for interleukin 6 (IL-6) and its receptor (IL-6R) in peripheral nerve regeneration in vivo. We first observed that cultured mouse embryonic dorsal root ganglia exhibited dramatic neurite extension by simultaneous addition of IL-6 and soluble IL-6R (sIL-6R), a complex that is known to interact with and activate a signal transducing receptor component, gp130. After injury in the hypoglossal nerve in adult mice by ligation, immunoreactivity to IL-6 was upregulated in Schwann cells at the lesional site as well as in the cell bodies of hypoglossal neurons in the brain stem. In the latter, upregulation of the immunoreactivity to IL-6R was also observed. Regeneration of axotomized hypoglossal nerve in vivo was significantly retarded by the administration of anti-IL-6R antibody. Surprisingly, accelerated regeneration of the axotomized nerve was achieved in transgenic mice constitutively expressing both IL-6 and IL-6R, as compared with nontransgenic controls. These results suggest that the IL-6 signal may play an important role in nerve regeneration after trauma in vivo.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology Antigens, CD/biosynthesis,immunology,physiology Cells, Cultured Embryo, Mammalian Ganglia, Spinal/drug effects,immunology,physiology Gene Expression Regulation Hypoglossal Nerve/immunology,physiology Immunoglobulin G/pharmacology Interleukin-6/biosynthesis,pharmacology Mice Mice, Inbred ICR Nerve Regeneration/immunology Neurites/drug effects,immunology,physiology Neurons/drug effects,immunology,physiology Receptors, Interleukin/biosynthesis,immunology,physiology Receptors, Interleukin-6
Chemicals
Antibodies, Monoclonal Antigens, CD Immunoglobulin G Interleukin-6 Receptors, Interleukin Receptors, Interleukin-6
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hirota H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kiyama H
Kishimoto T
Taga T
References (43)
43 references, click to expand
  1. Production of hybridoma growth factor by human monocytes.
    Eur J Immunol. 1987 Oct;17(10):1411-6 PMID: 3500054
  2. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin.
    Nature. 1986 Nov 6-12;324(6092):73-6 PMID: 3491322
  3. Production of B cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients.
    J Exp Med. 1988 Jul 1;168(1):449-53 PMID: 3135367
  4. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130.
    Cell. 1989 Aug 11;58(3):573-81 PMID: 2788034
  5. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy.
    Nature. 1990 May 31;345(6274):440-1 PMID: 2342575
  6. Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis.
    J Exp Med. 1990 Jun 1;171(6):2001-9 PMID: 2112585
  7. Molecular cloning and expression of an IL-6 signal transducer, gp130.
    Cell. 1990 Dec 21;63(6):1149-57 PMID: 2261637
  8. Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures.
    Neuroscience. 1991;40(2):445-52 PMID: 2027469
  9. Preparation of soluble murine IL-6 receptor and anti-murine IL-6 receptor antibodies.
    J Immunol. 1991 Jul 1;147(1):168-73 PMID: 2051018
  10. The receptor for ciliary neurotrophic factor.
    Science. 1991 Jul 5;253(5015):59-63 PMID: 1648265
  11. Neuropoietic cytokines in the hematopoietic fold.
    Neuron. 1991 Aug;7(2):197-208 PMID: 1714745
  12. Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production.
    J Neuroimmunol. 1991 Sep;33(3):227-36 PMID: 1874973
  13. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130.
    EMBO J. 1991 Oct;10(10):2839-48 PMID: 1915266
  14. Regulation of IL-6 expression by oncostatin M.
    J Immunol. 1991 Oct 1;147(7):2175-80 PMID: 1918953
  15. Immunolocalization of ciliary neuronotrophic factor in adult rat sciatic nerve.
    Glia. 1992;5(1):25-32 PMID: 1531807
  16. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor.
    Science. 1992 Mar 13;255(5050):1434-7 PMID: 1542794
  17. Cholinergic differentiation factor (CDF/LIF) promotes survival of isolated rat embryonic motoneurons in vitro.
    Neuron. 1992 Apr;8(4):737-44 PMID: 1567622
  18. The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons.
    Neuron. 1992 May;8(5):983-93 PMID: 1375039
  19. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130.
    Cell. 1992 Jun 26;69(7):1121-32 PMID: 1617725
  20. Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration.
    J Cell Biol. 1992 Jul;118(1):139-48 PMID: 1618901
  21. Interleukin-6 as a neurotrophic factor for promoting the survival of cultured catecholaminergic neurons in a chemically defined medium from fetal and postnatal rat midbrains.
    Neurosci Res. 1992 May;13(4):267-80 PMID: 1321390
  22. Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy.
    Nature. 1992 Aug 6;358(6386):502-4 PMID: 1641039
  23. Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo.
    Neuron. 1992 Aug;9(2):295-305 PMID: 1497895
  24. Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte-macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction.
    Blood. 1992 Sep 1;80(5):1190-8 PMID: 1381237
  25. Interleukin-6 and its receptor: a paradigm for cytokines.
    Science. 1992 Oct 23;258(5082):593-7 PMID: 1411569
  26. Molecular cloning and characterization of the rat liver IL-6 signal transducing molecule, gp130.
    Genomics. 1992 Nov;14(3):666-72 PMID: 1427893
  27. Functional inhibition of hematopoietic and neurotrophic cytokines by blocking the interleukin 6 signal transducer gp130.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10998-1001 PMID: 1438305
  28. Cytokine receptors and signal transduction.
    FASEB J. 1992 Dec;6(15):3387-96 PMID: 1334470
  29. LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor.
    Science. 1993 Jun 18;260(5115):1805-8 PMID: 8390097
  30. The alphas, betas, and kinases of cytokine receptor complexes.
    Cell. 1993 Aug 27;74(4):587-90 PMID: 8395346
  31. Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction.
    J Immunol. 1993 Sep 1;151(5):2555-61 PMID: 8360477
  32. Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes.
    J Neuroimmunol. 1993 Aug;47(1):23-34 PMID: 8376546
  33. Interleukin-6 and transforming growth factor-beta 1 mRNAs are induced in rat facial nucleus following motoneuron axotomy.
    Eur J Neurosci. 1993 Jul 1;5(7):775-81 PMID: 8281289
  34. Trophic support of motoneurons: physiological, pathophysiological, and therapeutic implications.
    Exp Neurol. 1993 Nov;124(1):47-55 PMID: 8282079
  35. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain.
    Eur J Neurosci. 1993 Nov 1;5(11):1426-35 PMID: 8287192
  36. Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve.
    Neuron. 1994 Jan;12(1):191-204 PMID: 7507340
  37. Cytokine signal transduction.
    Cell. 1994 Jan 28;76(2):253-62 PMID: 8293462
  38. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle.
    Cell. 1994 Feb 11;76(3):493-504 PMID: 8313470
  39. Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways.
    Mech Dev. 1994 Feb;45(2):163-71 PMID: 8199053
  40. Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF.
    Science. 1994 Aug 19;265(5175):1107-10 PMID: 8066451
  41. Interleukin-6 production by Schwann cells and induction in sciatic nerve injury.
    J Neurochem. 1995 Feb;64(2):850-8 PMID: 7830079
  42. Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):4862-6 PMID: 7539136
  43. Elevated levels of the 26K human hybridoma growth factor (interleukin 6) in cerebrospinal fluid of patients with acute infection of the central nervous system.
    Clin Exp Immunol. 1988 Feb;71(2):320-3 PMID: 3349651
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.6.2627
Published
1996-06-01
Pages
2627-34
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192614
Subset
IM
Corrections
CommentIn
PMID: 8676061
External Links
PubMed source DOI: 10.1084/jem.183.6.2627 PMC Full Text View journal details
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