Activation of gp 130 by IL‐6/soluble IL‐6 receptor induces neuronal differentiation

März, Pia; Herget, Thomas; Lang, Elisabeth; Otten, U.; Rose-John, Stefan

doi:10.1111/j.1460-9568.1997.tb01705.x

Cited by 96 publications

(86 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In order to demonstrate the role of BTG2 TIS21/PC3 in NGF-induced differentiation, PC12-18 and PC12-27 lines were treated, either with NGF alone or with a combination of IPTG and NGF (100 ng/ml). Neuronal differentiation was estimated by neurite outgrowth which was correlated with enhanced levels of the neuron-specific marker of differentiation aenolase (data not shown) (Vinores et al, 1981;Marz et al, 1997). After NGF treatment 20% of PC12-18 and PC12-27 lines developed neurites, whereas after IPTG/NGF treatment, up to 80% of cells differentiated (Figure 3a,b).…”

Section: Effects Of Btg2 Tis21/pc3 Expression On Pc12 Differentiationmentioning

confidence: 92%

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

et al. 2002

View full text Add to dashboard Cite

The p53-transcriptional target, BTG2 TIS21/PC3 , was previously identified as an antiproliferative gene. However, the precise biological functions of the protein product remain to be elucidated. BTG2 TIS21/PC3 expression is induced in vivo during neurogenesis, and the gene is transiently expressed in vitro in rat pheochromocytoma PC12 cells after induction of neuronal differentiation by addition of nerve growth factor (NGF). These observations suggest that BTG2 TIS21/PC3 is functionally significant during the neuronal differentiation process. To test this hypothesis, a vector that expressed BTG2 TIS21/PC3 under the control of an inducible promoter was introduced into PC12 cells. Growth arrest and differentiation in response to NGF were greatly enhanced by BTG2 TIS21/PC3 overexpression. Furthermore, an antisense oligonucleotide complementary to BTG2 TIS21/PC3 mRNA, which was able to inhibit endogenous BTG2 TIS21/PC3 expression, triggered programmed cell death in differentiated PC12 cells. These observations confirm that BTG2 TIS21/PC3 expression promotes neuronal differentiation and that it is required for survival of terminally differentiated cells.

show abstract

Section: Effects Of Btg2 Tis21/pc3 Expression On Pc12 Differentiationmentioning

confidence: 92%

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Furthermore, the above complex was also able to reduce infarct size. IL-6/sIL-6R complex has been reported to have various functions in the central nervous system, the hematopoietic system, and other tissues; [1][2][3][4][5][6] however, the effect of the complex in myocardial infarction has not been directly assessed so far. This is the first report of the possible therapeutic effects of IL-6/sIL-6R complex in reperfused myocardial infarction; our results suggest the possible use of this complex in the clinical treatment of reperfused myocardial infarction as well as other cardiac diseases involving apoptosis such as myocarditis and heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] Classically, many soluble receptors are used to inhibit ligand signaling of the native receptor. 7 However, soluble IL-6R acts as an agonist of IL-6 activity.…”

mentioning

confidence: 99%

“…17,18 In target cells expressing a small or no available number of membrane-bound IL-6R but expressing gp130, exogenously added IL-6 fail to exert its functions; however, coadministration of soluble IL-6R with IL-6 induces IL-6-mediated functions. 1,5 Although gp130 is expressed on cardiomyocytes, 9,19 whether cardiomyocytes express IL-6R is controversial. Saito et al 9 reported that cardiomyocytes did not express IL-6R, while Youker et al showed that IL-6 activated IL-6 signal pathway in cardiomyocytes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis

Matsushita

Iwanaga

Oda

et al. 2005

Laboratory Investigation

View full text Add to dashboard Cite

Apoptosis of cardiomyocytes plays an important role in reperfusion injury following myocardial infarction. Conversely, interleukin-6 (IL-6)-a potent cytokine-inhibits myeloma cell apoptosis by activating GP130 through the IL-6 receptor (IL-6R). We hypothesized that the IL-6/soluble IL-6R complex can inhibit myocardial apoptosis, and limit infarct size in reperfused acute myocardial infarction. Anesthetized rats were randomly divided into five groups: sham, coronary occlusion and reperfusion rats administered IL-6/soluble IL-6R complex, IL-6 alone, soluble IL-6R (sIL-6R) alone, or a control vehicle. Rats were subjected to 30 min occlusion of the left coronary artery followed by 3 h reperfusion. After reperfusion, the hearts were excised. For detection and quantification of apoptosis, gel electrophoresis of extracted genomic DNA and TUNEL method of paraffin sections were performed. The percentage of the infarct area was measured using tetrazolium chloride staining. The cardiomyocyte apoptosis analysis revealed that apoptosis in the reperfused myocardium was inhibited only in the complex group. Furthermore, the percentage of the infarct area out of the area at risk was remarkably reduced in the complex group (23.871.8%), compared with that in the vehicle (37.973.7%), the IL-6 (40.771.0%), or the sIL-6R (37.572.4%) groups (P ¼ 0.0002). No significant differences were observed among the vehicle, IL-6, and sIL-6R groups. The IL-6/soluble IL-6 receptor complex inhibits cardiomyocyte apoptosis in reperfused acute myocardial infarction. It possibly reduces irreversible reperfusion injury.

show abstract

“…Members of the family, which includes IL-6 itself, ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF), are upregulated after injury. The activity of neuropoietic cytokines has been associated not only with the control of innate immunity and activation of Schwann cells but also with cell survival, differentiation and axonal regeneration of neurons in the CNS and PNS (Saadat et al, 1989;Kopf et al, 1994;Murphy et al, 1995;Hirota et al, 1996;März et al, 1997März et al, , 1998Sendtner et al, 1997;Zhong et al, 1999;Cafferty et al, 2001Cafferty et al, , 2004Shuto et al, 2001;Cao et al, 2006;Wilms et al, 2007;Lara-Ramirez et al, 2008;Spooren et al, 2011;Smith et al, 2012;Zigmond, 2012). This qualifies neuropoietic cytokines as potentially important regulators of axonal regeneration also after nerve lesion.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Nerve Regeneration and NGF-Dependent Neurite Outgrowth of Adult Sensory Neurons Converge on STAT3 Phosphorylation Downstream of Neuropoietic Cytokine Receptor gp130

Quarta¹,

Baeumer²,

Scherbakov

et al. 2014

J. Neurosci.

View full text Add to dashboard Cite

After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration.After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130 Ϫ/Ϫ mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130 Ϫ/Ϫ compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130 Ϫ/Ϫ mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin.Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons.

show abstract

Activation of gp 130 by IL‐6/soluble IL‐6 receptor induces neuronal differentiation

Cited by 96 publications

References 58 publications

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

Interleukin-6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis

Peripheral Nerve Regeneration and NGF-Dependent Neurite Outgrowth of Adult Sensory Neurons Converge on STAT3 Phosphorylation Downstream of Neuropoietic Cytokine Receptor gp130

Contact Info

Product

Resources

About