Cytokine Secretion by Multiple Sclerosis Monocytes

Rudick, Richard A.; Ransohoff, Richard M.

doi:10.1001/archneur.1992.00530270079022

Cited by 72 publications

(22 citation statements)

References 13 publications

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“…Both X-ALD and MS are demyelinating diseases with the involvement of proinflammatory cytokines in the manifestation of white matter inflammation. Several studies demonstrating the induction of proinflammatory cytokines at the protein or mRNA level in cerebrospinal fluid and brain tissue of MS patients have established an association of proinflammatory cytokines (TNF-␣, IL-1␤, IL-2, IL-6, and IFN-␥) with the inflammatory loci in MS (33)(34)(35). Recent documentation of the presence of TNF-␣, IL-1␤, and IFN-␥ in X-ALD brain has revealed the neuroinflammatory character of this disease (36,37).…”

Section: Dna Fragmentation In Banked Humanmentioning

confidence: 99%

Cytokine-mediated Induction of Ceramide Production Is Redox-sensitive

Singh

Pahan

Khan

et al. 1998

Journal of Biological Chemistry

195

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The present study underlines the importance of reactive oxygen species in cytokine-mediated degradation of sphingomyelin (SM) to ceramide. Treatment of rat primary astrocytes with tumor necrosis factor-␣ (TNF-␣) or interleukin-1␤ led to marked alteration in cellular redox (decrease in intracellular GSH) and rapid degradation of SM to ceramide. Interestingly, pretreatment of astrocytes with N-acetylcysteine (NAC), an antioxidant and efficient thiol source for glutathione, prevented cytokine-induced decrease in GSH and degradation of sphingomyelin to ceramide, whereas treatment of astrocytes with diamide, a thiol-depleting agent, alone caused degradation of SM to ceramide. Moreover, potent activation of SM hydrolysis and ceramide generation were observed by direct addition of an oxidant like hydrogen peroxide or a prooxidant like aminotriazole. Similar to NAC, pyrrolidinedithiocarbamate, another antioxidant, was also found to be a potent inhibitor of cytokineinduced degradation of SM to ceramide indicating that cytokine-induced hydrolysis of sphingomyelin is redoxsensitive. Besides astrocytes, NAC also blocked cytokine-mediated ceramide production in rat primary oligodendrocytes, microglia, and C 6 glial cells. Inhibition of TNF-␣-and diamide-mediated depletion of GSH, elevation of ceramide level, and DNA fragmentation (apoptosis) in primary oligodendrocytes by NAC, and observed depletion of GSH, elevation of ceramide level, and apoptosis in banked human brains from patients with neuroinflammatory diseases (e.g. X-adrenoleukodystrophy and multiple sclerosis) suggest that the intracellular level of GSH may play a critical role in the regulation of cytokine-induced generation of ceramide leading to apoptosis of brain cells in these diseases.

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Section: Dna Fragmentation In Banked Humanmentioning

confidence: 99%

Cytokine-mediated Induction of Ceramide Production Is Redox-sensitive

Singh

Pahan

Khan

et al. 1998

Journal of Biological Chemistry

195

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“…Many authors suggested that the immune system deregulation has an important paper in the mediation of the inflammatory injuries, in the central scope. the immune misbalance in Ms has been demonstrated in the cellular immune response as well as in the humoral 4,5 and, even though there is not a known associated gene to this disease, it has been verified a clear polygenic genetic susceptibility 6,7 .…”

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confidence: 99%

C3c intrathecal synthesis evaluation in patients with multiple sclerosis

Padilla-Docal¹,

Dorta‐Contreras²,

Fundora-Hernández³

et al. 2007

Arq. Neuro-Psiquiatr.

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-Introduction: Multiple sclerosis (Ms) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). Objective: to determine if the complement system might be involved in the Ms immunopathogeny favouring the mechanism intervening in the myelin destruction. Method: samples of sera and csF from twelve patients with a diagnosis of Ms obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of c3c and albumin in sera and in csF were quantified using radial immunodiffusion plates. Results: High values over 80% of intrathecal synthesis were obtained except in one of the patients. Conclusion: Intrathecal synthesis of c3c and its liberation to the csF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process Key words: cytotoxicity, complement, multiple sclerosis, hypersensibility, immunopathogenicity, reibergram.evaluación de la síntesis intratecal de C3c en pacientes con esclerosis múltiple resuMeN -Introducción: La esclerosis múltiple (eM) es una enfermedad crónica, inflamatoria y progresiva del sistema nervioso central que cursa con la aparición de lesiones inflamatorias focales en la sustancia blanca cerebral, en las que lo más llamativo es la pérdida de mielina (desmielinización). Objetivo: conocer si el sistema de complemento puede estar involucrado en la inmunopatogenia de la eM favoreciendo los mecanismos que median la destrucción de la mielina. Método: se colectaron muestras de suero y Lcr de doce pacientes con diagnóstico de eM obtenidas en el momento del ingreso al inicio del brote. se cuantificaron los niveles de c3c y albúmina en suero y en Lcr en placas de inmunodifusión radial. Resultados: se obtuvieron altos valores que superan el 80% de síntesis intratecal, menos en uno de los pacientes. Conclusion: La síntesis intratecal de c3c y su liberación al Lcr significa que ha sucedido la activación del sistema de complemento en alguna de las dos vías y que una vez cumplidas sus funciones biológicas, ha sufrido un proceso de degradación y liberación al Lcr en forma de c3c.PALABrAs-cLAve: citotoxicidad, complemento, esclerosis múltiple, hipersensibilidad, inmunopatogenia, reibergrama.

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“…The pathogenesis of multiple sclerosis (MS) is a complex, multicellular process in which the infiltration of both monocytes and lymphocytes plays a key role (34,39). Despite considerable experimental evidence and scientific opinion pointing to a role for T cells in the pathology of MS, there is little consensus on the role played by the peripheral blood monocyte.…”

mentioning

confidence: 99%

Expression of Urokinase Plasminogen Activator Receptor on Monocytes from Patients with Relapsing-Remitting Multiple Sclerosis: Effect of Glatiramer Acetate (Copolymer 1)

Balabanov

Lisak

Beaumont

et al. 2001

Clin Diagn Lab Immunol

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which peripheral blood monocytes play an important role. We have previously reported that patients with chronic progressive MS (CPMS) have significantly increased numbers of circulating monocytes which express the urokinase plasminogen activator receptor (uPAR). In the present study, we examined the expression of uPAR on monocytes in patients with relapsing-remitting multiple sclerosis (

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Cytokine Secretion by Multiple Sclerosis Monocytes

Cited by 72 publications

References 13 publications

Cytokine-mediated Induction of Ceramide Production Is Redox-sensitive

Cytokine-mediated Induction of Ceramide Production Is Redox-sensitive

C3c intrathecal synthesis evaluation in patients with multiple sclerosis

Expression of Urokinase Plasminogen Activator Receptor on Monocytes from Patients with Relapsing-Remitting Multiple Sclerosis: Effect of Glatiramer Acetate (Copolymer 1)

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