title: L-kynurenine-induced apoptosis in human NK cells is mediated by reactive oxygen species.
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.
authors.affiliation: Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Park
authors.forename: Yeong-Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Cho
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Yang
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000037:antagonists & inhibitors; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007737:Kynurenine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000975:Antioxidants; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017382:Reactive Oxygen Species; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007737:Kynurenine; D045304:Cytochromes c; D053148:Caspase 3