Ceramide signalling and the immune response

Ballou, Leslie R.; Laulederkind, Stanley J. F.; Rosloniec, Edward F.; Raghow, Rajendra

doi:10.1016/0005-2760(96)00004-5

Cited by 239 publications

(164 citation statements)

References 113 publications

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“…Sphingomyelin pathway has been claimed to be involved in the apoptotic process and ceramide, the product of sphingomyelin hydrolysis by sphingomyelinase, appears to be a functional mediator of this pathway Ballou et al, 1996;Testi, 1996). In this present study, we demonstrated for the first time that ceramide induces apoptosis in FRTL-5 thyroid cells, although it has been known to induce apoptosis in hematopoietic cells, fibroblast (Obeid et al, 1993), neurons (Brugg et al, 1996) and reproductive cells (Kaipia et al, 1996;Witty et al, 1996).…”

Section: Discussionsupporting

confidence: 46%

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Park¹,

Kim²,

Han³

et al. 1999

Exp Mol Med

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Ceramide, a product of sphingomyelin hydrolysis, is now recognized as an intracellular lipid messenger, which mediates the effects of extracellular agents on cellular growth, differentiation and apoptosis. Recently, ceramide has been implicated in the regulation of phospholipase D (PLD). In this study, we examined the effects of ceramide on the activity and mRNA level of PLD during apoptotic process in FRTL-5 thyroid cells. C 2 -ceramide (N-acetyl sphingosine) induced apoptosis in FRTL-5 thyroid cells. Fluorescent staining showed that ceramide induced the typical features of apoptosis including condensed or fragmented nuclei. DNA fragmentation was also observed by agarose gel electrophoresis. Flow cytometric cell cycle analysis showed more clearly that ceramide induced apoptotic cell death in FRTL-5 thyroid cells. The treatment of FRTL-5 thyroid cells with thyroid-stimulating hormone (TSH) resulted in an increased PLD activity in a dose-and time-dependent manner. However, the TSH-induced increase in PLD activity was down-regulated within 2 h after ceramide treatment. Furthermore, the levels of PLD mRNA were found to be decreased throughout apoptotic process as inferred by reverse transcription-polymerase chain reaction. However, the decreases in PLD mRNA levels were not correlated with those in PLD activities after ceramide treatment. Taken together, these data suggest that ceramide inhibits the PLD activity in an early apoptotic phase and down-regulation of the levels of PLD mRNA may be implicated in apoptotic process in FRTL-5 thyroid cells.

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Section: Discussionsupporting

confidence: 46%

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Park¹,

Kim²,

Han³

et al. 1999

Exp Mol Med

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“…Some studies suggest that in GD type 1 patients the accumulation of the immunogenic components in macrophages, such as ceramide and sphingolipids, causes cellular activation and consequently ChT secretion, which may mediate the immune response involved (Ballou et al 1996;van Eijk et al 2005). Increased ChT activity was also recorded in several other diseases, such as Niemann-Pick (Brinkman et al 2005), GM1 gangliosidosis , b-thalassemia (Barone et al 1999), sarcoidosis (Boot et al 2010), malaria (Barone et al 2003), atherosclerosis (Artieda et al 2003;Boot et al 1999), and fungal and bacterial infections (Iyer et al 2009;Labadaridis et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

et al. 2012

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“…In addition, activated macrophages directly release sphingomyelinase (19). The list of biological effects attributable to ceramide is continually expanding and includes roles in the regulation of cell proliferation and differentiation, inflammation, and apoptosis, dependent on cell type and concentrations of ceramide (20,21).…”

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confidence: 99%

Ceramide-Induced TCR Up-Regulation

Menné

Lauritsen

Dietrich

et al. 2000

The Journal of Immunology

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The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected to increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase inhibitors indicated that ceramide-induced TCR up-regulation was most probably mediated by serine/threonine protein phosphatase 2A. Analyses of T cell variants demonstrated that TCR up-regulation was dependent on the presence of an intact CD3γ L-based motif and thus acted on TCR engaged in the recycling pathway. Finally, we showed that TCR up-regulation probably plays a physiological role by increasing T cell responsiveness. Thus, by affecting the TCR recycling kinetics, T cells have the potential both to up- and down-regulate TCR expression and thereby adjust T cell responsiveness.

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Ceramide signalling and the immune response

Cited by 239 publications

References 113 publications

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

Ceramide-Induced TCR Up-Regulation

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