Inhibition of T cell apoptosis by IFN-β rapidly reverses nuclear translocation of protein kinase C-δ
✍ Scribed by Dagmar Scheel-Toellner; Darrell Pilling; Arne N. Akbar; Deborah Hardie; Giovanna Lombardi; Mike Salmon; Janet M. Lord
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 176 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Type I interferons rescue activated human T cells from cytokine deprivation-induced apoptosis. Our data now show that IFN-g also rapidly inhibits apoptotic signals induced through the Fas receptor (CD95) in human T cells. To identify upstream signaling elements that could be targets of IFN-g , we have studied protein kinase C (PKC). PKC-ˇis actively involved in the regulation of apoptosis and immunofluorescence staining revealed that early in apoptosis PKC-ˇaccumulated in the nucleus. Addition of IFN-g to T cells already deprived of survival factors or treated with anti-Fas antibody caused a rapid retranslocation of PKC-ˇaway from the nucleus. Furthermore, the generation of a constitutively active catalytic fragment by cleavage of PKC-ˇby caspase 3 occurred only after translocation of full-length PKC-ˇto the nucleus. IFN-g also inhibited caspase 3 and the proteolytic activation of PKC-ˇ. We conclude from these studies that nuclear translocation of PKC-ˇis an early event in T cell apoptosis and that IFN-g rapidly reverses this process.