Selective up-regulation of caspase-3 gene expression following TCR engagement.

Abstract:

:Activation-induced cell death (AICD) in T lymphocytes depends on the expression of Fas-ligand, which triggers the apoptotic process after binding to its receptor Fas. This leads to the activation of cysteine proteases of the caspase family and especially of caspase-3, a critical effector protein during AICD. We have previously observed the up-regulation of caspase-3 expression in effector but not memory T cells stimulated in vivo. In this study, we further characterized the regulation of caspase expression following T cell receptor (TCR) signaling and demonstrate that a three-fold increase in caspase-3 mRNA levels was observed by semi-quantitative and real-time RT-PCR analysis. Caspase-3 expression was selectively increased among five different caspases following TCR stimulation, as assessed by RNase protection assay. Real-time RT-PCR analysis demonstrated that a three-fold up-regulation in caspase-3 mRNA levels was observed following TCR triggering, whereas caspase-8 mRNA levels remained unchanged. The increase in caspase-3 mRNA levels occurred before cleavage and activation of caspase-3 and in the absence of apoptosis. TCR-mediated induction in caspase-3 expression was not dependent on STAT1 activation, since following stimulation of KOX-14 cells the transcription factor was not phosphorylated. Together, these results show that TCR activation triggers the selective increase in caspase-3 mRNA levels, independently of caspase activity and the induction of apoptosis.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Sabbagh L,Bourbonnière M,Sékaly RP,Cohen LY

doi

10.1016/j.molimm.2004.12.011

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

1345-54

issue

11

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(05)00009-X

journal_volume

42

pub_type

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