Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury

Gardiner, Natalie J.; Cafferty, William B. J.; Slack, Sarah E.; Thompson, S.W.N.

doi:10.1046/j.1471-4159.2002.01101.x

Cited by 67 publications

(59 citation statements)

References 58 publications

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“…2A). Neurons also stained strongly for LIF-R at these time points with diffuse staining in the dendrites and strong nuclear staining as has been reported in cells previously (Gardiner et al, 2002). LIF immunoreactivity was present in both neurons and GFAP + cells ( Fig.…”

Section: Lif Is Required For Development Of Hippocampal Gliasupporting

confidence: 84%

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Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Cohen

Fields

2008

Neuron Glia Biol.

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Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuronglial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P2Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF −/− mice had reduced numbers of astrocytes and activity-dependent neuron-glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP.

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Section: Lif Is Required For Development Of Hippocampal Gliasupporting

confidence: 84%

“…By 12 DIV, LIF-R was still present in astrocyte processes, OPCs and neurons. Note that strong expression of LIF-R is present in the nucleus with more diffuse staining in processes (see Gardiner et al, 2002). Scale bar = 25 µm.…”

Section: Fig 1 Differentiation Of Gpc In Hippocampal Culturementioning

confidence: 98%

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Cohen

Fields

2008

Neuron Glia Biol.

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“…The receptor for leukemia inhibitory factor is upregulated in a subset of nociceptive neurons following nerve injury. It is involved in nerve regeneration of small diameter sensory neurons and could be responsible for Cl Ϫ accumulation in nociceptive neurons (Cafferty et al, 2001;Gardiner et al, 2002). Cell-specific regulation of receptor expression appears to be a major event in the control cellular responses to nerve injury and repair.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, peripheral injury-induced IL-6 is able to promote regeneration within the CNS (Cafferty et al, 2004;Cao et al, 2006). Since the IL-6 signal-transducing ␤ receptor, gp130, is ubiquitously expressed in sensory neurons, the specificity of IL-6 signaling is mainly mediated by tissue-specific constitutive IL-6 ␣ receptor, IL-6R, expression and/or local actions of soluble IL-6R (Gardiner et al, 2002;Andratsch et al, 2009). Although the effects of IL-6 are well established in nerve regeneration, the cellular expression of IL-6R in the dorsal root ganglia is unknown.…”

Section: Introductionmentioning

confidence: 99%

An Autocrine Neuronal Interleukin-6 Loop Mediates Chloride Accumulation and NKCC1 Phosphorylation in Axotomized Sensory Neurons

Pieraut¹,

Lucas²,

Sangari³

et al. 2011

J. Neurosci.

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The cation-chloride cotransporter NKCC1 plays a fundamental role in the central and peripheral nervous systems by setting the value of intracellular chloride concentration. Following peripheral nerve injury, NKCC1 phosphorylation-induced chloride accumulation contributes to neurite regrowth of sensory neurons. However, the molecules and signaling pathways that regulate NKCC1 activity remain to be identified. Functional analysis of cotransporter activity revealed that inhibition of endogenously produced cytokine interleukin-6 (IL-6), with anti-mouse IL-6 antibody or in IL-6 Ϫ/Ϫ mice, prevented chloride accumulation in a subset of axotomized neurons. Nerve injury upregulated the transcript and protein levels of IL-6 receptor in myelinated, TrkB-positive sensory neurons of murine lumbar dorsal root ganglia. Expression of phospho-NKCC1 was observed mainly in sensory neurons expressing IL-6 receptor and was absent from IL-6 Ϫ/Ϫ dorsal root ganglia. The use of IL-6 receptor blocking-function antibody or soluble IL-6 receptor, together with pharmacological inhibition of Janus kinase, confirmed the role of neuronal IL-6 signaling in chloride accumulation and neurite growth of a subset of axotomized sensory neurons. Cell-specific expression of interleukin-6 receptor under pathophysiological conditions is therefore a cellular response by which IL-6 contributes to nerve regeneration through neuronal NKCC1 phosphorylation and chloride accumulation.

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“…For example, IL-6 knock-out mice have impaired peripheral nerve regeneration , whereas mice that constitutively overexpress IL-6 and its soluble receptor (sIL-6R) show enhanced PNS regeneration (Hirota et al, 1996). The gp130 receptor exists in sensory neurons (Gardiner et al, 2002), and evidence to date suggests that gp130 receptor activation may be an integral component of the enhanced growth state that follows conditioning peripheral nerve lesions Snider et al, 2002). In this study, we focused on the role that injury-induced IL-6 may play in the intrinsic growth status and associated regeneration of injured sensory neuron collaterals within ascending dorsal column pathways.…”

Section: Introductionmentioning

confidence: 99%

Conditioning Injury-Induced Spinal Axon Regeneration Fails in Interleukin-6 Knock-Out Mice

Cafferty¹,

Gardiner²,

Das³

et al. 2004

J. Neurosci.

242

165

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Regeneration of injured adult sensory neurons within the CNS is essentially abortive, attributable in part to lesion-induced or revealed inhibitors such as the chondroitin sulfate proteoglycans and the myelin inhibitors (Nogo-A, MAG, and OMgp). Much of this inhibition may be overcome by boosting the growth status of sensory neurons by delivering a conditioning lesion to their peripheral branches. Here, we identify a key role for the lesion-induced cytokine interleukin-6 (IL-6) in mediating conditioning lesion-induced enhanced regeneration of injured dorsal column afferents. In adult mice, conditioning injury to the sciatic nerve 1 week before bilateral dorsal column crush resulted in regeneration of dorsal column axons up to and beyond the injury site into host CNS tissue. This enhanced growth state was accompanied by an increase in the expression of the growth-associated protein GAP43 in preinjured but not intact dorsal root ganglia (DRGs). Preconditioning injury of the sciatic nerve in IL-6 Ϫ/Ϫ mice resulted in the total failure in regeneration of dorsal column axons consequent on the lack of GAP43 upregulation after a preconditioning injury. DRGs cell counts and cholera toxin ␤ subunit labeling revealed that impaired regeneration in knock-out mice was unrelated to cell loss or a deficit in tracer transport. In vitro, exogenous IL-6 boosted sensory neuron growth status as evidenced by enhanced neurite extension. This effect required NGF or NT-3 but not soluble IL-6 receptor as cofactors. Evidence of conditioning lesion-enhanced growth status of DRGs cells can also be observed in vitro as an earlier and enhanced rate of neurite extension; this phenomenon fails in IL-6 Ϫ/Ϫ mice preinjured 7 d in vivo. We suggest that injury-induced IL-6 upregulation is required to promote regeneration within the CNS. Our results indicate that this is achieved through a boosted growth state of dorsal column projecting sensory neurons.

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Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury

Cited by 67 publications

References 58 publications

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

An Autocrine Neuronal Interleukin-6 Loop Mediates Chloride Accumulation and NKCC1 Phosphorylation in Axotomized Sensory Neurons

Conditioning Injury-Induced Spinal Axon Regeneration Fails in Interleukin-6 Knock-Out Mice

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