The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7): a survival factor in activated human T cells.
The effects of interleukin 7 (IL-7) on apoptosis in interleukin 2 (IL-2)-dependent, activated, primary, human T lymphocytes (hT cells) was examined. IL-7 (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA profile and fragmentation. IL-2 also acted as a mitogen in these T cells. Both cytokines abrogated the dexamethasone-induced stimulation of Caspase 3 and prevented the cleavage of poly (ADP-ribose) polymerase (PARP), a substrate for the Caspase 3. IL-7 upregulated the expression of Bc1xL and counteracted the downregulation of this anti-apoptotic protein by the synthetic glucocorticoid, dexamethasone. Bcl-2 protein expression was uupregulated by IL-7 with or without dexamethasone, but Bc1-2 was expressed at a much lower level than BclxL in these cells. Levels of Bax did not markedly change on either cytokine stimulation or dexamethasone treatment. An unidentified 23-kDa band, which was recognized by the anti-Bc1-2 antibody, was induced by dexamthasone and suppressed by IL-7 and IL-2. This protein was subject to independent regulation as compared to the p26 Bc1-2 protein, suggesting that it may be a novel factor, possibly involved in the regulation of apoptosis. A clear role for IL-7 as a survival factor for cytokine withdrawal and glucocorticoid induced apoptosis in activated primary hT cells is implicated. In addition, regulation of BclxL and downstream inhibition of Caspase 3 activity may mediate this rescue signal.
Amos
C L
CL
Department of Human Metabolism and Clinical Biochemistry, Cellular Signalling, Institute of Endocrinology, University of Sheffield Medical School, Sheffield, S10 2RX, U.K.
Woetmann
A
A
Nielsen
M
M
Geisler
C
C
Odum
N
N
Brown
B L
BL
Dobson
P R
PR
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D005938:Glucocorticoids; D007376:Interleukin-2; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D003907:Dexamethasone; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases