期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 11, 期 8, 页码 932-938出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2011.02.005
关键词
NK cell; ROS; IDO; L-Kynurenine; Apoptosis
资金
- Ministry of Education, Science and Engineering, Korea [R13-2007-023-00000-0]
- Korean Government (MOEHRD) [KRF-2008-331-E00094]
- National Research Foundation of Korea [331-2008-1-E00094, 과06A1206] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Recent studies have shown that indoleamine 2,3-dioxygenase (IDO) plays a pivotal role in the modulation of immune response against tumor and virus infection. Here we demonstrate the pro-apoptotic effect of L-kynurenine, a tryptophan catabolite of IDO, on human NK cell line, NK92 MI. Treatment with L-kynurenine dose-dependently induced growth inhibition and apoptosis in NK92 MI cells. Treatment with the antioxidant NAC completely protected cells from L-kynurenine-induced apoptosis. Moreover, we found that treatment with Z-VAD-fmk and ZB4 slightly inhibited L-kynurenine-induced apoptosis, suggesting that L-kynurenine-induced apoptosis in NK cells occurs primarily through an ROS mediated pathway. We observed that the presence of NAC blocks cytochrome c release and activation of caspase-3 during L-kynurenine-induced apoptosis. Overall, we conclude that L-kynurenine resulting from 100 can cause cell death via ROS pathway in NK cells. Our findings provide a new insight into the interaction between NK cells and IDO positive cancer cells in regulating immune responses. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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