TY - JOUR

T1 - The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7): a survival factor in activated human T cells

AU - Amos, C L

AU - Woetmann, A

AU - Nielsen, M

AU - Geisler, C

AU - Odum, N

AU - Brown, B. L.

AU - Dobson, P R

N1 - Keywords: Apoptosis; Caspase 3; Caspases; Cell Survival; Cells, Cultured; Dexamethasone; Enzyme Activation; Gene Expression Regulation; Glucocorticoids; Humans; Interleukin-2; Interleukin-7; Lymphocyte Activation; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; T-Lymphocytes; bcl-X Protein

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

U2 - 10.1006/cyto.1998.0351

DO - 10.1006/cyto.1998.0351

M3 - Journal article

C2 - 9770327

VL - 10

SP - 662

EP - 668

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 9

ER -