The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the transcription factor NF-AT

Gómez, Javier; Martı́nez-A, Carlos; González, Ana; García, Alphonse; Rebollo, Angelita

doi:10.1038/sj.onc.1202049

Cited by 41 publications

(31 citation statements)

References 46 publications

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“…The low IL-2 levels that were encountered in cultured, activated CD4 ϩ T cells from HD patients may explain the high susceptibility of activated CD4 ϩ T cells to become apoptotic in the presence of stimulatory agents such as oxLDL (via Fas pathway). Inhibition of IL-2 synthesis during T cell activation has been shown to downregulate Bcl-2 expression and to inactivate Bcl-2 through phosphorylation (39,40). In this system, IL-2 deprivation upon oxLDL exposure might result in a gradual disappearance of Bcl-2 that is responsible, at least in part, for the higher Fas-mediated apoptotic rate of activated CD4 ϩ T cells in HD patients.…”

Section: Discussionmentioning

confidence: 99%

Oxidized Low-Density Lipoproteins Activate CD4+ T Cell Apoptosis in Patients with End-Stage Renal Disease through Fas Engagement

Meier¹,

Spertini

Blanc

et al. 2007

Journal of the American Society of Nephrology

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Oxidized LDL (oxLDL) are cytotoxic to vascular cells, but their possible toxic action on T cells from patients with ESRD has not been evaluated. oxLDL concentrations were measured and compared in patients who were on long-term hemodialysis (HD), in patients who had ESRD and were on continuous ambulatory peritoneal dialysis, in nondialyzed patients with chronic kidney disease, and in age-and gender-matched control subjects. In parallel, the proliferative capacity of CD69

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Section: Discussionmentioning

confidence: 99%

Oxidized Low-Density Lipoproteins Activate CD4+ T Cell Apoptosis in Patients with End-Stage Renal Disease through Fas Engagement

Meier¹,

Spertini

Blanc

et al. 2007

Journal of the American Society of Nephrology

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“…We have previously reported that Bcl-2 is expressed in IL-2-stimulated cells and Bcl-x in IL-4-cultured cells (22). When IL-4-maintained cells are deprived of lymphokine, they undergo apoptosis (Fig.…”

Section: Bad Associates With Lipid Rafts In Il-4-stimulated Cellsmentioning

confidence: 99%

Segregation of Bad from Lipid Rafts Is Implicated in the Induction of Apoptosis

Ayllón

Fleischer

Cayla

et al. 2002

The Journal of Immunology

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Many molecules relocate subcellularly in cells undergoing apoptosis. Using coimmunoprecipitation experiments we demonstrate that Bad is not associated to 14-3-3 protein, suggesting a new mechanism for the control of the proapoptotic role of Bad. Here we show, by confocal microscopy and cellular fractionation, that Bad is attached to lipid rafts in IL-4-stimulated cells and thymocytes while associated with mitochondria in IL-4-deprived cells. Disruption of lipid rafts by methyl-β-cyclodextrin treatment induces segregation of Bad from rafts, which correlates with apoptosis. Our results suggest that the interaction of Bad with rafts is a dynamic process regulated by IL-4 and involved in the control of apoptosis.

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“…Recently, IL-2 stimulation of T cells has been shown to induce NFAT DNA binding activity (42). The DNA binding activity of NFAT was detected by EMSA as 2 bands (Fig.…”

Section: Cd8mentioning

confidence: 99%

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Adachi¹,

Amasaki²,

Miyatake³

et al. 2000

Journal of Biological Chemistry

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Differentiation of immature CD4؉ CD8 ؉ thymocytes to mature CD4 ؉ or CD8 ؉ T cells is induced by positive selection and appears to involve calcineurin-dependent activation of NFAT, a family of transcription factors. NFATx is predominantly expressed in CD4 ؉ CD8 ؉ thymocytes, whereas NFATp and NFATc are expressed at much lower levels in the thymus than in mature T cells. However, how or when each NFAT member is involved in the differentiation pathway is unclear. Using an in vitro model system where isolated CD4 ؉ CD8؉ thymocytes can survive and differentiate into semi-mature CD4-lineage T cells, we suggest that low calcineurin activity sustained for approximately 20 h is required for cell survival and differentiation. Accordingly, the DNA binding activity of NFAT slowly increased during the stimulation of 20 h to induce the differentiation. NFATx significantly contributed to the early rise, but the late increase was mostly due to NFATc activation. Meanwhile, the expression of NFATx mRNA decreased and that of NFATc mRNA increased. The DNA-binding activity of NFATp was detectable but low throughout the stimulation. NFATp became dominantly active after the semi-mature T cells differentiated into mature and activated CD4 T cells. These findings suggest that NFATx and NFATc successively play roles in T cell development.

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The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the transcription factor NF-AT

Cited by 41 publications

References 46 publications

Oxidized Low-Density Lipoproteins Activate CD4+ T Cell Apoptosis in Patients with End-Stage Renal Disease through Fas Engagement

Oxidized Low-Density Lipoproteins Activate CD4+ T Cell Apoptosis in Patients with End-Stage Renal Disease through Fas Engagement

Segregation of Bad from Lipid Rafts Is Implicated in the Induction of Apoptosis

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

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