IL-4-dependent induction of BCL-2 and BCL-X(L)IN activated T lymphocytes through a STAT6- and pi 3-kinase-independent pathway.

Aronica MA, Goenka S, Boothby M
Cytokine. 2000 12 (6): 578-87

PMID: 10843732 · DOI:10.1006/cyto.1999.0603

Both B and T lymphocytes require ongoing signals to maintain their viability. The pleiotropic cytokine interleukin (IL-) 4 plays an important role in the maintenance of activated T cells, perhaps reflecting induction of the anti-apoptotic genes Bcl-2 and Bcl-X(L). However, it is not known which of the signalling pathways known to link the IL-4 receptor with transcription regulation are required, or if the levels of Bcl-2/X induction under such physiologic conditions are sufficient to account for the anti-apoptotic effects of IL-4. We report here that although blockade of pathways (PI 3-kinase and pp70 S6 kinase) recruited by the IRS-1/2 adaptor proteins inhibited the anti-apoptotic function of IL-4, Bcl-2/X induction were normal. These findings were recapitulated in primary and culture-adapted T cells whose Stat6 signalling pathway also was defective. These results demonstrate that both the Stat6 and PI 3-kinase pathways can be dispensable for Bcl-2/X induction by IL-4, thus suggesting the involvement of an additional signal transduction pathway. Moreover, the preservation of Bcl-2/X induction despite inhibition of the anti-apoptotic function of IL-4 indicates that this cytokine activates additional protective mechanisms.

Copyright 2000 Academic Press.

MeSH Terms (25)

Androstadienes Animals bcl-X Protein Cell Division Cell Line Cell Survival Crosses, Genetic Enzyme Inhibitors Genes, bcl-2 Interleukin-4 Lymphocyte Activation Mice Mice, Knockout Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-bcl-2 Receptors, Interleukin-4 Recombinant Proteins Signal Transduction Sirolimus STAT6 Transcription Factor T-Lymphocytes, Cytotoxic Trans-Activators Transcriptional Activation Transfection Wortmannin

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