Abstract
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 IDO 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
Original language | English |
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Pages (from-to) | 932-938 |
Number of pages | 7 |
Journal | International Immunopharmacology |
Volume | 11 |
Issue number | 8 |
DOIs | |
Publication status | Published - 2011 Aug |
Externally published | Yes |
Keywords
- Apoptosis
- IDO
- L-Kynurenine
- NK cell
- ROS
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology