HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print August 20, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0407259v1 82/5/1344    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kanayama, A. Articles by Miyamoto, Y. Search for Related Content PubMed PubMed Citation Articles by Kanayama, A. Articles by Miyamoto, Y.

(Journal of Leukocyte Biology. 2007;82:1344-1352.)
© 2007 by Society for Leukocyte Biology

Apoptosis triggered by phagocytosis-related oxidative stress through FLIP_S down-regulation and JNK activation

Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba Japan

¹ Correspondence: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Bioscience Building 402, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. E-mail: kanayama-atsuhiro{at}k.u-tokyo.ac.jp

Tumor necrosis factor- (TNF-)-activated neutrophils phagocytose and eliminate bacteria by using such oxidants as hydrogen peroxide (H₂O₂) and hypochlorous acid (HOCl), which is produced from H₂O₂ by myeloperoxidase (MPO). Thereafter, neutrophils eventually undergo apoptosis to prevent excessive inflammation. However, it is unclear how this process is regulated. Here, we show that cotreatment of TNF--resistant neutrophilic HL-60 cells with taurine chloramine (TauCl), a detoxified form of HOCl, and TNF- renders them susceptible to apoptosis, mostly by preventing nuclear factor-B (NF-B) activation. Of several NF-B target genes tested, FLICE inhibitory protein short form (FLIP_S) was specifically down-regulated by TauCl. TNF-/TauCl cotreatment-induced apoptosis was largely blocked by stable expression of FLIP_S. Cotreatment with TNF- and H₂O₂ promoted apoptotic signaling via MPO activation and subsequent attenuation of FLIP_S expression. TNF- priming with H₂O₂ or bacteria caused MPO-dependent apoptosis in human neutrophils. However, FLIP_S knock-down by siRNA did not affect the viability of cells treated with TNF-, implying that TauCl may affect another pathway in TNF--driven apoptosis. Indeed, oxidization of thioredoxin-1 (Trx-1) by TauCl induced the activation of apoptosis signal-regulating kinase 1 (ASK1) and cJun N-terminal kinase (JNK), thereby triggering TNF--mediated apoptosis. Taken together, these results indicate that the antiapoptotic signaling induced by TNF- via NF-B activation can be altered to promote apoptosis via H₂O₂-MPO-mediated FLIP_S down-regulation and JNK activation.

Key Words: taurine chloramine • ASK1 • TNF

This article has been cited by other articles:

				D. El Kebir, L. Jozsef, W. Pan, and J. G. Filep Myeloperoxidase Delays Neutrophil Apoptosis Through CD11b/CD18 Integrins and Prolongs Inflammation Circ. Res., August 15, 2008; 103(4): 352 - 359. [Abstract] [Full Text] [PDF]