PMID- 23618907
OWN - NLM
STAT- MEDLINE
DCOM- 20131023
LR  - 20211203
IS  - 2041-4889 (Electronic)
VI  - 4
IP  - 4
DP  - 2013 Apr 25
TI  - Interleukin-6 contributes to CNS axon regeneration upon inflammatory stimulation.
PG  - e609
LID - 10.1038/cddis.2013.126 [doi]
AB  - Mature retinal ganglion cells (RGCs) do not normally regenerate injured axons and 
      undergo apoptosis after axotomy. Inflammatory stimulation (IS) in the eye 
      mediates neuroprotection and induces axon regeneration into the injured optic 
      nerve. Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) 
      have been identified as key mediators of these effects. Here, we investigated the 
      role of interleukin-6 (IL-6), another member of the glycoprotein 130-activating 
      cytokine family, as additional contributing factor. Expression of IL-6 was 
      markedly induced in the retina upon optic nerve injury and IS, and mature RGCs 
      expressed the IL-6 receptor. Treatment of cultured RGCs with IL-6 or specific 
      IL-6 receptor agonist, significantly increased neurite outgrowth janus 
      kinase/signal transducers and activators of transcription-3 (JAK/STAT3) and 
      phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) dependently. Moreover, 
      IL-6 reduced myelin, but not neurocan-mediated growth inhibition mammalian target 
      of rapamycin (mTOR) dependently in cultured RGCs. In vivo, intravitreal 
      application of IL-6 transformed RGCs into a regenerative state, enabling axon 
      regeneration beyond the lesion site of the optic nerve. On the other hand, 
      genetic ablation of IL-6 in mice significantly reduced IS-mediated myelin 
      disinhibition and axon regeneration in the optic nerve. Therefore, IL-6 
      contributes to the beneficial effects of IS and its disinhibitory effect adds an 
      important feature to the effects of so far identified IS-mediating factors. 
      Consequently, application of IL-6 or activation of its receptor might provide 
      suitable strategies for enhancing optic nerve regeneration.
FAU - Leibinger, M
AU  - Leibinger M
AD  - Department of Neurology, Heinrich-Heine-University of Dusseldorf, Merowingerplatz 
      1a, Dusseldorf, Germany.
FAU - Muller, A
AU  - Muller A
FAU - Gobrecht, P
AU  - Gobrecht P
FAU - Diekmann, H
AU  - Diekmann H
FAU - Andreadaki, A
AU  - Andreadaki A
FAU - Fischer, D
AU  - Fischer D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130425
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Interleukin-6)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Neurocan)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Axons/*physiology
MH  - Cells, Cultured
MH  - Ciliary Neurotrophic Factor/pharmacology
MH  - Female
MH  - Interleukin-6/*pharmacology
MH  - Janus Kinases/metabolism
MH  - Leukemia Inhibitory Factor/pharmacology
MH  - Myelin Sheath/metabolism
MH  - Nerve Regeneration/*drug effects
MH  - Neurocan/*metabolism
MH  - Optic Nerve/drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Interleukin-6/agonists/metabolism
MH  - Retinal Ganglion Cells/cytology/*drug effects/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3641349
EDAT- 2013/04/27 06:00
MHDA- 2013/10/24 06:00
PMCR- 2013/04/01
CRDT- 2013/04/27 06:00
PHST- 2013/04/27 06:00 [entrez]
PHST- 2013/04/27 06:00 [pubmed]
PHST- 2013/10/24 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - cddis2013126 [pii]
AID - 10.1038/cddis.2013.126 [doi]
PST - epublish
SO  - Cell Death Dis. 2013 Apr 25;4(4):e609. doi: 10.1038/cddis.2013.126.