Regulation of an oligodendrocyte progenitor cell line by the interleukin‐6 family of cytokines

Kahn, M.A.; Vellis, Jean de

doi:10.1002/glia.440120202

Cited by 126 publications

(84 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IL-6 has been reported to exert trophic effects on glial cells, including oligodendroglia themselves, producing increased expression of glial fibrillary-acidic protein (Kahn and De Vellis, 1994). Paradoxically, IL-6 increases intracellular calcium levels during NMDA-receptor activation, enhancing neurotoxicity and cell death in granular neurons (Qiu et al, 1998).…”

Section: Il-6: a Prototype Proinflammatory Cytokine Of The Cnsmentioning

confidence: 99%

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

Garver

Tamas

Holcomb

2003

Neuropsychopharmacol

133

View full text Add to dashboard Cite

Evidence of immune activation has occasionally, but not consistently, been reported in schizophrenia. Investigations of cytokine abnormalities in serum, and occasionally in CSF, have yielded inconsistent results, which have been difficult to resolve. In such studies, schizophrenia has been assumed to consist of a single process rather than a group of disorders. This study assesses differences in the proinflammatory cytokine, interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) in two previously delineated subtypes of schizophrenics ('delayed-responders' (DR) (n ¼ 23) and 'poor-responders' (PR) (n ¼ 8)) during periods of neuroleptic-free psychotic exacerbation, and in a comparison group of normal controls (n ¼ 14). The two response subtypes were separated by subsequent treatment response (greater/less than 60% reduction of SAPS scores from baseline during 6 months of systematic treatment). The IL-6 assay, a sandwich enzyme-linked immunosorbent assay, was sensitive and reliable to detect IL-6 levels in the CSF of all subjects. CSF IL-6 was found to be significantly higher in the DR than the PR (P ¼ 0.017) and the controls (P ¼ 0.013). In addition to supporting the concept of heterogeneity in schizophrenia, this study also provides evidence that a central immune process may be occurring centrally in one subtype of schizophrenia.

show abstract

Section: Il-6: a Prototype Proinflammatory Cytokine Of The Cnsmentioning

confidence: 99%

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

Garver

Tamas

Holcomb

2003

Neuropsychopharmacol

133

View full text Add to dashboard Cite

show abstract

“…Studies on primary cultures of O2A have shown that CNTF and LIF can induce conversion of O2A into astrocytes, as has been assessed by GFAP staining (Hughes et al, 1988;Lillien et al, 1990;Mayer et al, 1994;Gard et al, 1995a,b). Studies conducted on CG-4 also indicate a role for CNTF and LIF in the differentiation of progenitor cells towards astrocytes (Kahn and De Vellis, 1994;Kahn et al, 1997). Furthermore, CNTF and LIF are well known OL survival factors: CNTF has been shown to enhance OL survival after TNF-a treatment or removal of trophic factors, and LIF has also been shown to promote OL survival in vitro (Barres et al, 1993;Louis et al, 1993;Mayer et al, 1994;D.…”

Section: A Comparison Of Primary Ol and Cg-4mentioning

confidence: 99%

Mitogen‐activated protein kinase signalling in oligodendrocytes: a comparison of primary cultures and CG‐4

Stariha¹,

Kim²

2001

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Oligodendrocytes play a significant role in the central nervous system, as these cells are responsible for myelinating axons and allowing for the efficient conduction of nerve impulses. Therefore, any understanding we can gain about the functional biology of oligodendrocytes will give us important insights into demyelinating diseases such as multiple sclerosis, where oligodendrocytes and myelin are damaged or destroyed. Currently, much attention has focussed on the role of a family of mitogen-activated protein kinases in OL. This kinase family includes the extracellular signal-regulated protein kinases (ERKs), the stress-activated c-Jun N-terminal kinase (JNK), and the 38 kDa high osmolarity glycerol response kinase (p38). The actions of mitogen-activated protein kinases in oligodendrocytes appear to range from proliferation and cell survival to differentiation and cell death. In the past, studies on oligodendrocytes have been hampered by the difficulties inherent in producing large enough quantities of these cells for experimentation. This problem arises in large part due to the post-mitotic nature of mature oligodendrocytes. Over the years, a cell line known as Central Glia-4 (CG-4) has become a popular oligodendrocyte model due to its potentially unlimited capacity for self-renewal. In this review, we will look at the suitability of the Central Glia-4 cell line as an oligodendrocyte model, specifically in respect to studies on mitogen-activated protein kinase signalling in oligodendrocytes.

show abstract

“…Thus, increasing attention has been focused on the functional role of the hematopoietic cytokines belonging to the IL-6R family in the CNS. For instance, IL-6 promotes the differentiation of cortical precursor cells into oligodendrocytes and astrocytes (Kahn and De Vellis, 1994;Wagner, 1996;Bonni et al, 1997;Gruol and Nelson, 1997;Rajan and McKay 1998;Nakanishi et al, 2007), activates adult astrocytes (Campbell et al, 1993), and also functions as a neurotrophic and differentiation factor for neurons of the central and peripheral nervous system (Satoh et al, 1988;Gadient and Otten, 1997;März et al, 1997März et al, , 1998Schäfer et al, 1999;Thier et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 and Neural Stem Cells: More Than Gliogenesis

Islam

Gong

Rose-John

et al. 2009

MBoC

156

103

View full text Add to dashboard Cite

Besides its wide range of action as a proinflammatory cytokine in the immune system, interleukin-6 (IL-6) has also attracted much attention due to its influence on the nervous system. In the present study we show that the designer fusion protein H-IL-6, consisting of IL-6 and its specific receptor IL-6R-␣, but not IL-6 alone, mediates both neuro-as well as gliogenesis. Using immunocytochemistry, Western blot, and patch-clamp recording, we demonstrate that H-IL-6 induces the differentiation of neural stem cells (NSCs) specifically into glutamate-responsive neurons and two morphological distinctive astroglia cell types. H-IL-6 -activated neurogenesis seems to be induced by the MAPK/CREB (mitogenactivated protein kinase/cAMP response element-binding protein) cascade, whereas gliogenesis is mediated via the STAT-3 (signal transducers and activators of transcription protein-3) signaling pathway. Our finding that IL-6 mediates both processes depending on its specific soluble receptor sIL-6R-␣ has implications for the potential treatment of neurodegenerative diseases. INTRODUCTIONIn recent years it has been noted that the adult brain has "self-repair-capacity" to replace lost neurons in several selected regions of the CNS such as the olfactory bulb, hippocampus, adult human subependymal zone, and the cortex. Active neurogenesis occurs in the subgranular zone (SGZ) of the hippocampal dentate gyrus, and in the subventricular zone (SVZ) of the lateral ventricles (Kempermann and Gage, 1999;Gage, 2000;Okano, 2002). Neural stem cells (NSCs) within these neurogenic regions can self-renew, proliferate, and differentiate into neurons or glia, providing a reservoir for replacement of cells lost during normal cell turnover and after brain injury. Newborn neurons and glia then migrate to appropriate regions in the brain and integrate into neuronal circuits (Brazel and Rao, 2004;Campos, 2004;Ming and Song, 2005;Reynolds and Rietze, 2005). Recent findings show that impairment of neurogenesis is sufficient to deteriorate learning and memory, hinting that abnormalities in the proliferation and differentiation of NSCs could play a role in the pathogenesis of cognitive disorders such as Alzheimer's disease (Shors, 2004). The question facing modern medicine is how best to use NSCs to produce functional recovery in neurodegenerative disorders in the aging brain (Arvidsson et al., 2002;Sugaya, 2005;Tanne, 2005).The interleukin-6 (IL-6) receptor family is comprised of multisubunit receptors associated with a common receptor subunit, the transmembrane protein gp130 (Taga and Kishimoto, 1997;Heinrich et al., 2003). Natural soluble forms of those integral-membrane receptors have been described for numerous cytokines (Jones and Rose-John, 2002). Although most of them act as antagonists by competing for their ligands with the membrane bound receptors, the soluble IL-6R (sIL-6R), which is generated by limited proteolysis (shedding) or alternative splicing, behaves as an agonist (Jones and Rose-John, 2002;Rose-John and Neurath, 2004). Thus, the co...

show abstract

Regulation of an oligodendrocyte progenitor cell line by the interleukin‐6 family of cytokines

Cited by 126 publications

References 52 publications

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

Mitogen‐activated protein kinase signalling in oligodendrocytes: a comparison of primary cultures and CG‐4

Interleukin-6 and Neural Stem Cells: More Than Gliogenesis

Contact Info

Product

Resources

About