Tumor necrosis factor-α up-regulates Bcl-2 expression and decreases calcium-dependent apoptosis in human B cell lines

Group I and Epstein–Barr virus-negative Burkitt's lymphoma cell lines and the B104 lymphoma cell line which expresses a phenotype of immature B cells undergo apoptosis after cross-linking of their surface Ig receptors or after exposure to a calcium ionophore. We show here that tumor necrosis fa...

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Bibliographic Details
Published in:International immunology 1995-04, Vol.7 (4), p.533-540
Main Authors: Genestier, Laurent, Bonnefoy-Berard, Nathalie, Rouault, Jean-Pierre, Flacher, Monique, Revillard, Jean-Pierre
Format: Article
Language:English
Subjects:
apoptosis
Apoptosis - drug effects
B cell lines
B-Lymphocytes - metabolism
Bcl-2
Calcineurin
Calcium - antagonists & inhibitors
Calcium - physiology
Calmodulin-Binding Proteins - pharmacology
Cell Line
Cyclosporine - pharmacology
Enzyme Activation
Humans
Life Sciences
Phosphoprotein Phosphatases - pharmacology
protein kinase C
Protein Kinase C - metabolism
Proto-Oncogene Proteins - biosynthesis
Proto-Oncogene Proteins - drug effects
Proto-Oncogene Proteins c-bcl-2
Tetradecanoylphorbol Acetate - pharmacology
Tumor Necrosis Factor-alpha - physiology
tumor necrosis factor-α
Up-Regulation
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Summary:Group I and Epstein–Barr virus-negative Burkitt's lymphoma cell lines and the B104 lymphoma cell line which expresses a phenotype of immature B cells undergo apoptosis after cross-linking of their surface Ig receptors or after exposure to a calcium ionophore. We show here that tumor necrosis factor (TNF)-α protects these B cell lines against Ca2+-dependent apoptosis. Protection was associated with up-regulatlon of bcl-2 mRNA and protein expression. The increase of Bcl-2 expression induced by TNF-α was inhibited by chelerythrine, a specific inhibitor of protein kinase C (PKC), suggesting that Bcl-2 expression was dependent on PKC activation. Furthermore, we show that phorbol esters and cyclosporin A (CsA), which prevent Ca2+-dependent apoptosis, up-regulated Bcl-2 expression. The effect of CsA on Bcl-2 expression is controlled by calcineurin since we have shown that FK506 but not rapamycin had the same effect on Bcl-2 expression, whereas okadaic acid, an inhibitor of phosphatases 1, 2A and 2C, was ineffective. These data provide direct evidence that TNF-α prevents Ca2+-dependent apoptosis by a Bcl-2-dependent mechanism mediated by PKC.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/7.4.533