L-Kynurenine-induced apoptosis in human NK cells is mediated by reactive oxygen species

Hyunkeun Song, Hyunjin Park, Yeong Seok Kim, Kwang Dong Kim, Hyun Kyung Lee, Dae Ho Cho, Jae Wook Yang, Dae Young Hur

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 languageEnglish
Pages (from-to)932-938
Number of pages7
JournalInternational Immunopharmacology
Volume11
Issue number8
DOIs
Publication statusPublished - 2011 Jan 1
Externally publishedYes

Keywords

  • Apoptosis
  • IDO
  • L-Kynurenine
  • NK cell
  • ROS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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