PMID- 17709401 OWN - NLM STAT- MEDLINE DCOM- 20071206 LR - 20211203 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 82 IP - 5 DP - 2007 Nov TI - Apoptosis triggered by phagocytosis-related oxidative stress through FLIPS down-regulation and JNK activation. PG - 1344-52 AB - Tumor necrosis factor-alpha (TNF-alpha)-activated neutrophils phagocytose and eliminate bacteria by using such oxidants as hydrogen peroxide (H(2)O(2)) and hypochlorous acid (HOCl), which is produced from H(2)O(2) 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-alpha-resistant neutrophilic HL-60 cells with taurine chloramine (TauCl), a detoxified form of HOCl, and TNF-alpha renders them susceptible to apoptosis, mostly by preventing nuclear factor-kappaB (NF-kappaB) activation. Of several NF-kappaB target genes tested, FLICE inhibitory protein short form (FLIP(S)) was specifically down-regulated by TauCl. TNF-alpha/TauCl cotreatment-induced apoptosis was largely blocked by stable expression of FLIP(S). Cotreatment with TNF-alpha and H(2)O(2) promoted apoptotic signaling via MPO activation and subsequent attenuation of FLIP(S) expression. TNF-alpha priming with H(2)O(2) 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-alpha, implying that TauCl may affect another pathway in TNF-alpha-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-alpha-mediated apoptosis. Taken together, these results indicate that the antiapoptotic signaling induced by TNF-alpha via NF-kappaB activation can be altered to promote apoptosis via H(2)O(2)-MPO-mediated FLIP(S) down-regulation and JNK activation. FAU - Kanayama, Atsuhiro AU - Kanayama A AD - Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Bioscience Building 402, 5-1-5 Kashiwanoha, Kashiwa, Chiba, Japan. kanayama-atsuhiro@k.u-tokyo.ac.jp FAU - Miyamoto, Yusei AU - Miyamoto Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070820 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Antiviral Agents) RN - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein) RN - 0 (CFLAR protein, human) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 1EQV5MLY3D (Taurine) RN - 51036-13-6 (N-chlorotaurine) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.7 (Peroxidase) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5) RN - EC 3.4.22.- (Caspases) SB - IM MH - Antiviral Agents/pharmacology MH - Apoptosis/*physiology MH - Blotting, Western MH - CASP8 and FADD-Like Apoptosis Regulating Protein/*metabolism MH - Caspases/metabolism MH - Cell Survival/drug effects MH - Down-Regulation MH - Enzyme Activation MH - Gene Expression Regulation, Neoplastic MH - HL-60 Cells MH - Humans MH - Hydrogen Peroxide/pharmacology MH - JNK Mitogen-Activated Protein Kinases/*metabolism MH - Kidney/cytology/metabolism MH - MAP Kinase Kinase Kinase 5/metabolism MH - NF-kappa B/metabolism MH - Neutrophils/drug effects/metabolism MH - *Oxidative Stress MH - Peroxidase/metabolism MH - *Phagocytosis MH - Protein Serine-Threonine Kinases/antagonists & inhibitors MH - Taurine/analogs & derivatives/pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2007/08/22 09:00 MHDA- 2007/12/07 09:00 CRDT- 2007/08/22 09:00 PHST- 2007/08/22 09:00 [pubmed] PHST- 2007/12/07 09:00 [medline] PHST- 2007/08/22 09:00 [entrez] AID - jlb.0407259 [pii] AID - 10.1189/jlb.0407259 [doi] PST - ppublish SO - J Leukoc Biol. 2007 Nov;82(5):1344-52. doi: 10.1189/jlb.0407259. Epub 2007 Aug 20.