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PMID: 16707807 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 26 ·No. 20 ·2006-05-17 ·Pages 5565-73

Cao Z, Gao Y, Bryson JB, Hou J, Chaudhry N, Siddiq M, Martinez J, Spencer T, Carmel J, Hart RB, Filbin MT

Abstract

Lesioning the peripheral branch of a dorsal root ganglion (DRG) neuron before injury of the central branch of the same neuron enables spontaneous regeneration of these spinal axons. This effect is cAMP and transcription dependent. Here, we show that the cytokine interleukin-6 (IL-6) is upregulated in DRG neurons after either a conditioning lesion or treatment with dibutyryl-cAMP. In culture, IL-6 allows neurons to grow in the presence of inhibitors of regeneration present in myelin. Importantly, intrathecal delivery of IL-6 to DRG neurons blocks inhibition by myelin both in vitro and in vivo, effectively mimicking the conditioning lesion. Blocking IL-6 signaling has no effect on the ability of cAMP to overcome myelin inhibitors. Consistent with this, IL-6-deficient mice respond to a conditioning lesion as effectively as wild-type mice. We conclude that IL-6 can mimic both the cAMP effect and the conditioning lesion effect but is not an essential component of either response.

MeSH Terms
Animals Animals, Newborn Bucladesine/pharmacology CHO Cells Cells, Cultured Cricetinae Disease Models, Animal Female Ganglia, Spinal/cytology,drug effects,metabolism Growth Cones/drug effects,metabolism Growth Inhibitors/antagonists & inhibitors,metabolism Interleukin-6/metabolism,pharmacology Male Mice Mice, Knockout Myelin Proteins/antagonists & inhibitors,metabolism Nerve Regeneration/drug effects,physiology Neurons, Afferent/cytology,drug effects,metabolism Peripheral Nerve Injuries Peripheral Nerves/cytology,metabolism Rats Rats, Long-Evans Sciatic Neuropathy/drug therapy,metabolism,physiopathology Up-Regulation/drug effects,physiology
Chemicals
Growth Inhibitors Interleukin-6 Myelin Proteins Bucladesine
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Cao Zixuan
Department of Biological Sciences, Hunter College, The City University of New York, New York, New York 10021, USA.
Gao Ying
Bryson J Barney
Hou Jianwei
Chaudhry Nagarathnamma
Siddiq Mustafa
Martinez Jennifer
Spencer Tim
Carmel Jason
Hart Ronald B
Filbin Marie T
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0815-06.2006
Published
2006-05-17
Pages
5565-73
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6675293
Subset
IM
Grants
NINDS NIH HHS · NS37060 · United States
NINDS NIH HHS · NS41073 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0815-06.2006 PMC Full Text View journal details
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