Inhibition of T cell apoptosis by IFN-beta rapidly reverses nuclear translocation of protein kinase C-delta.
Type I interferons rescue activated human T cells from cytokine deprivation-induced apoptosis. Our data now show that IFN-beta 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-beta, we have studied protein kinase C (PKC). PKC-delta is actively involved in the regulation of apoptosis and immunofluorescence staining revealed that early in apoptosis PKC-delta accumulated in the nucleus. Addition of IFN-beta to T cells already deprived of survival factors or treated with anti-Fas antibody caused a rapid retranslocation of PKC-delta away from the nucleus. Furthermore, the generation of a constitutively active catalytic fragment by cleavage of PKC-delta by caspase 3 occurred only after translocation of full-length PKC-delta to the nucleus. IFN-beta also inhibited caspase 3 and the proteolytic activation of PKC-delta. We conclude from these studies that nuclear translocation of PKC-delta is an early event in T cell apoptosis and that IFN-beta rapidly reverses this process.
Scheel-Toellner
D
D
MRC Centre for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, GB.
Pilling
D
D
Akbar
A N
AN
Hardie
D
D
Lombardi
G
G
Salmon
M
M
Lord
J M
JM
D017209:Apoptosis; D001693:Biological Transport, Active; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D034882:Lamins; D009687:Nuclear Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism
D007527:Isoenzymes; D034882:Lamins; D009687:Nuclear Proteins; D019014:fas Receptor; D016899:Interferon-beta; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases