IL-4-dependent induction of Bcl-2 and Bcl-XL in activated T lymphocytes through a Stat6-and PI 3-kinase-independent pathway

被引:31
作者
Aronica, MA
Goenka, S
Boothby, M [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Sch Med, Dept Microbiol & Immunol,Med Ctr N AA4214B, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Sch Med, Dept Med,Allergy Pulm & Crit Care Med Div, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Sch Med, Dept Med,Rheumatol Div, Nashville, TN 37232 USA
关键词
D O I
10.1006/cyto.1999.0603
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-2PX 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. (C) 2000 Academic Press.
引用
收藏
页码:578 / 587
页数:10
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