Increased Levels of Tumor Necrosis Alpha and Soluble Vascular Endothel Adhesion Molecule-1 in the Cerebrospinal Fluid of Patients with Connective Tissue Diseases and Multiple Sclerosis

Baraczka, Krisztina; Pozsonyi, T; Szüts, I Ldikó; Ormos, G.; Nékám, K

doi:10.1556/amicr.50.2003.4.3

Cited by 14 publications

(10 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inflammatory processes within the CNS involve activated microglia, astrocytes, macrophages and lymphocytes releasing a plethora of anti-and pro-inflammatory cytokines including both IFN-gamma and TNF-alpha [43]. This occurs in a number of inflammatory neurodegenerative disorders, including multiple sclerosis, in which high levels of TNF-alpha within cerebrospinal fluid and infiltration of IFN-gamma secreting activated T-cells into the brain is seen [44][45][46]. Neuroinflammation and subsequent microglial activation plays an important role in the pathogenesis of several neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine Induced Regulation of Superoxide Dismutase 3 Expression by Human Mesenchymal Stem Cells

Kemp

Gray

Mallam

et al. 2010

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Increasing evidence suggests that bone marrow derived-mesenchymal stem cells (MSCs) have neuroprotective properties and a major mechanism of action is through their capacity to secrete a diverse range of potentially neurotrophic or anti-oxidant factors. The recent discovery that MSCs secrete superoxide dismutase 3 (SOD3) may help explain studies in which MSCs have a direct anti-oxidant activity that is conducive to neuroprotection in both in vivo and in vitro. SOD3 attenuates tissue damage and reduces inflammation and may confer neuroprotective effects against nitric oxide-mediated stress to cerebellar neurons; but, its role in relation to central nervous system inflammation and neurodegeneration has not been extensively investigated. Here we have performed a series of experiments showing that SOD3 secretion by human bone marrow-derived MSCs is regulated synergistically by the inflammatory cytokines TNF-alpha and IFN-gamma, rather than through direct exposure to reactive oxygen species. Furthermore, we have shown SOD3 secretion by MSCs is increased by activated microglial cells. We have also shown that MSCs and recombinant SOD are able to increase both neuronal and axonal survival in vitro against nitric oxide or microglial induced damage, with an increased MSC-induced neuroprotective effect evident in the presence of inflammatory cytokines TNF-alpha and IFN-gamma. We have shown MSCs are able to convey these neuroprotective effects through secretion of soluble factors alone and furthermore demonstrated that SOD3 secretion by MSCs is, at least, partially responsible for this phenomenon. SOD3 secretion by MSCs maybe of relevance to treatment strategies for inflammatory disease of the central nervous system.

show abstract

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine Induced Regulation of Superoxide Dismutase 3 Expression by Human Mesenchymal Stem Cells

Kemp

Gray

Mallam

et al. 2010

Stem Cell Rev and Rep

View full text Add to dashboard Cite

show abstract

“…The occurrence of the latter could be explained by studies documenting Na + /K + ATPase failure [51,118,239], reverse action of Na + -Ca 2+ exchanger, intra-axonal calcium accumulation, and a subsequent Ca 2+ -dependent apoptosis [10,77,218]. In addition, other inflammatory mediators such as TNF-␣, IFN-␥, and IL-1␤ are abundant in the cerebrospinal fluid (CSF) of MS patients [8,97,186] and can provide a second route toward neurodegeneration: the so-called inflammationinduced synaptopathy [23]. In fact, these molecules can act by upregulating the excitatory glutamatergic transmission [109,132,215], a phenomenon that is already documented in MS patients [32,196,210,216] or downregulating the inhibitory GABAergic transmission [215]; both of which could be the final pathway toward an aberrant synaptic transmission and irreversible neurodegenerative damage [32,210] and may contribute to fatigue perception.…”

Section: Physiological and Neurochemical Correlates Of Ms Fatiguementioning

confidence: 99%

“…The presence of immunological dysregulation at the basis of the disease [8,97,186] might also raise the possibility of a contributory role of inflammatory cytokines in the pathophysiology of MS fatigue. This was previously emphasized by the influence of inflammation on neurodegeneration (i.e.…”

Section: Neuroimmune Correlates Of Ms Fatiguementioning

confidence: 99%

Fatigue in multiple sclerosis – Insights into evaluation and management

Ayache

Chalah

2017

Neurophysiologie Clinique/Clinical Neurophysiology

126

View full text Add to dashboard Cite

“…[60][61][62][63] In particular, TNFa, IFNg and IL-1b are all potential candidates for such an action, as they are released in response to microglial activation, 49,50,64,65 increase in the CSF of MS patients, [66][67][68] and have been shown in vitro to enhance excitatory synaptic transmission 60,62,69 and downregulate…”

Section: Role Of Inflammatory Cytokines In Synaptic Alterationmentioning

confidence: 99%

The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis

Muzio²,

et al. 2009

View full text Add to dashboard Cite

Multiple sclerosis (MS) has been classically regarded as a disorder of the white matter of the central nervous system (CNS). However, early alterations of the neuronal compartment occurring in this disorder are partially independent of demyelination. Soluble inflammatory cytokines and glutamate have been proposed as major determinants of neurodegeneration in MS as well as in its experimental animal model, namely experimental autoimmune encephalomyelitis (EAE). The relationship between these two major determinants has been largely elusive. In recent years, unexpected connections have emerged between immune cells and soluble cytokines on the one hand, and synaptic transmission and neurodegeneration on the other. Neurophysiological recordings have recently shown that glutamate-mediated excitatory postsynaptic currents are enhanced during the early phase of EAE, because of altered expression and phosphorylation of AMPA receptors and the downregulation of the immediate early gene Arc/Arg3.1. The synaptic alterations occurring during neuroinflammatory diseases are largely mediated by inflammatory cytokines released from infiltrating T cells and from activated microglia, and are responsible, at least in part, for irreversible dendritic pathology. Collectively, the data covered in this review article suggest that CNS-confined inflammation in MS is associated with the release of soluble molecules, which are capable of altering excitatory synaptic transmission and, finally, of stimulating secondary neurodegenerative gray matter pathology.

show abstract

Increased Levels of Tumor Necrosis Alpha and Soluble Vascular Endothel Adhesion Molecule-1 in the Cerebrospinal Fluid of Patients with Connective Tissue Diseases and Multiple Sclerosis

Cited by 14 publications

References 26 publications

Inflammatory Cytokine Induced Regulation of Superoxide Dismutase 3 Expression by Human Mesenchymal Stem Cells

Inflammatory Cytokine Induced Regulation of Superoxide Dismutase 3 Expression by Human Mesenchymal Stem Cells

Fatigue in multiple sclerosis – Insights into evaluation and management

The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis

Contact Info

Product

Resources

About