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TNF-alpha induces transient resistance to Fas-induced apoptosis in eosinophilic acute myeloid leukemia cells.
Cell Mol Immunol. 2007 Feb; 4(1):43-52.CM

Abstract

Tumor necrosis factor alpha (TNF-alpha) has been recognized as an activator of nuclear factor kappaB (NF-kappaB), a factor implicated in the protection of many cell types from apoptosis. We and others have presented evidence to suggest that Fas-induced apoptosis may be an important aspect of the resolution of inflammation, and that delayed resolution of inflammation may be directly associated with NF-kappaB-dependent resistance to Fas. Because TNF-alpha activates NF-kappaB in many cell types including inflammatory cells such as eosinophils, we examined effects of TNF-alpha signaling on the Fas-mediated killing of an eosinophilic cell line AML14. While agonist anti-Fas (CH11) treatment induced apoptosis in AML14 cells, no significant cell death occurred in response to TNF-alpha alone. Electrophoretic mobility shift assay (EMSA) revealed that TNF-alpha induced NF-kappaB transactivation in AML14 cells in a time- and dose-dependent fashion, and subsequent supershift assays indicated that the translocated NF-kappaB was the heterodimer p65 (RelA)/p50. Pre-treatment of cells with TNF-alpha dramatically decreased the CH11-induced cell death in a transient fashion, accompanied by suppression of activation of caspase-8 and caspase-3 activation. Inhibition of NF-kappaB transactivation by inhibitors, BAY 11-7085 and parthenolide, reversed the suppression of Fas-mediated apoptosis by TNF-alpha. Furthermore, TNF-alpha up-regulated X-linked inhibitor of apoptosis protein (XIAP) transiently and XIAP levels were correlated with the temporal pattern of TNF-alpha protection against Fas-mediated apoptosis. This finding suggested that TNF-alpha may contribute to the prolonged survival of inflammatory cells by suppression of Fas-mediated apoptosis, the process involved with NF-kappaB transactivation, anti-apoptotic XIAP up-regulation and caspase suppression.

Authors+Show Affiliations

Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. yqin@medicine.bsd.uchicago.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17349210

Citation

Qin, Yimin, et al. "TNF-alpha Induces Transient Resistance to Fas-induced Apoptosis in Eosinophilic Acute Myeloid Leukemia Cells." Cellular & Molecular Immunology, vol. 4, no. 1, 2007, pp. 43-52.
Qin Y, Auh S, Blokh L, et al. TNF-alpha induces transient resistance to Fas-induced apoptosis in eosinophilic acute myeloid leukemia cells. Cell Mol Immunol. 2007;4(1):43-52.
Qin, Y., Auh, S., Blokh, L., Long, C., Gagnon, I., & Hamann, K. J. (2007). TNF-alpha induces transient resistance to Fas-induced apoptosis in eosinophilic acute myeloid leukemia cells. Cellular & Molecular Immunology, 4(1), 43-52.
Qin Y, et al. TNF-alpha Induces Transient Resistance to Fas-induced Apoptosis in Eosinophilic Acute Myeloid Leukemia Cells. Cell Mol Immunol. 2007;4(1):43-52. PubMed PMID: 17349210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-alpha induces transient resistance to Fas-induced apoptosis in eosinophilic acute myeloid leukemia cells. AU - Qin,Yimin, AU - Auh,Sogyong, AU - Blokh,Lyubov, AU - Long,Catherine, AU - Gagnon,Isabelle, AU - Hamann,Kimm J, PY - 2007/3/14/pubmed PY - 2007/6/2/medline PY - 2007/3/14/entrez SP - 43 EP - 52 JF - Cellular & molecular immunology JO - Cell Mol Immunol VL - 4 IS - 1 N2 - Tumor necrosis factor alpha (TNF-alpha) has been recognized as an activator of nuclear factor kappaB (NF-kappaB), a factor implicated in the protection of many cell types from apoptosis. We and others have presented evidence to suggest that Fas-induced apoptosis may be an important aspect of the resolution of inflammation, and that delayed resolution of inflammation may be directly associated with NF-kappaB-dependent resistance to Fas. Because TNF-alpha activates NF-kappaB in many cell types including inflammatory cells such as eosinophils, we examined effects of TNF-alpha signaling on the Fas-mediated killing of an eosinophilic cell line AML14. While agonist anti-Fas (CH11) treatment induced apoptosis in AML14 cells, no significant cell death occurred in response to TNF-alpha alone. Electrophoretic mobility shift assay (EMSA) revealed that TNF-alpha induced NF-kappaB transactivation in AML14 cells in a time- and dose-dependent fashion, and subsequent supershift assays indicated that the translocated NF-kappaB was the heterodimer p65 (RelA)/p50. Pre-treatment of cells with TNF-alpha dramatically decreased the CH11-induced cell death in a transient fashion, accompanied by suppression of activation of caspase-8 and caspase-3 activation. Inhibition of NF-kappaB transactivation by inhibitors, BAY 11-7085 and parthenolide, reversed the suppression of Fas-mediated apoptosis by TNF-alpha. Furthermore, TNF-alpha up-regulated X-linked inhibitor of apoptosis protein (XIAP) transiently and XIAP levels were correlated with the temporal pattern of TNF-alpha protection against Fas-mediated apoptosis. This finding suggested that TNF-alpha may contribute to the prolonged survival of inflammatory cells by suppression of Fas-mediated apoptosis, the process involved with NF-kappaB transactivation, anti-apoptotic XIAP up-regulation and caspase suppression. SN - 1672-7681 UR - https://www.unboundmedicine.com/medline/citation/17349210/TNF_alpha_induces_transient_resistance_to_Fas_induced_apoptosis_in_eosinophilic_acute_myeloid_leukemia_cells_ L2 - http://www.cmi.ustc.edu.cn/4/1/43.pdf DB - PRIME DP - Unbound Medicine ER -