期刊
CELLULAR IMMUNOLOGY
卷 241, 期 1, 页码 14-25出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2006.07.006
关键词
ANT3; IL-4; T cell survival; ErK; NF-kappa B
We have identified mitochondrial adenine nucleotide translocase (ANT)3 as a novel target up-regulated by IL-4 in human T cells. The IL-4-induced ANT3 expression is dependent on tyrosine kinase, NF-kappa B, PI3K/Akt, and Erk pathways. In fact, IL-4 induced specific activation of NF-kappa B, Akt, and Erk in Jurkat T cells and partially rescued these cells from dexamethasone-induced apoptosis. The IL-4-mediated T cell survival was blocked by inhibitors of tyrosine kinase, NF-kappa B, PI3K/Akt, and Erk. During the IL-4-induced T cell rescue, there was a concomitant increase in ANT3, nuclear NF-kappa B, and Bcl-2 and a decrease in ANTI, I-kappa B, and mitochondrial Bax-alpha levels. Importantly, overexpression of ANT3 effectively protected T cells from dexamethasone-induced apoptosis, while forced expression of ANTI caused apoptosis. In contrast, siRNA knock-out of ANT3 expression induced T cell apoptosis and blocked the IL-4-mediated cell survival. Together these results suggest that ANT3 has a potential role in Th cell survival and immune cell homeostasis. (c) 2006 Elsevier Inc. All rights reserved.
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