IL-4-induced upregulation of adenine nucleotide translocase 3 and its role in Th cell survival from apoptosis.
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-kappaB, PI3K/Akt, and Erk pathways. In fact, IL-4 induced specific activation of NF-kappaB, 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-kappaB, PI3K/Akt, and Erk. During the IL-4-induced T cell rescue, there was a concomitant increase in ANT3, nuclear NF-kappaB, and Bcl-2 and a decrease in ANT1, I-kappaB, and mitochondrial Bax-alpha levels. Importantly, overexpression of ANT3 effectively protected T cells from dexamethasone-induced apoptosis, while forced expression of ANT1 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.
Jang
Ji-Young
JY
Department of Biological Science and Institute for Basic Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Lee
Choong-Eun
CE
D033781:Adenine Nucleotide Translocator 3 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D019169:Jurkat Cells; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D033781:Adenine Nucleotide Translocator 3; C508598:IL4 protein, human; D015847:Interleukin-4