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Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway in human beta cells by Fas-associated death domain and nuclear factor kappaB.
Hum Immunol. 2005 Jul; 66(7):799-809.HI

Abstract

Transfectants of human CM and NES2Y beta cell lines and primary islets transfected by FADD-DN (dominant-negative form of Fas-associated death domain), a mutant of FADD and/or a superrepressor of nuclear factor kappaB (NF-kappaB) (AdIkappaB(SA)2), were examined for their susceptibility to the TRAIL (TNF-related apoptosis-inducing ligand)-induced death signal pathway, compared with controls, wild-type cells, and vector transfectants in caspase fluorescence, Western blot, electrophoretic mobility shift, apoptosis, and cytotoxicity assays. FADD-DN inhibited caspase-8 activation induced by TRAIL in the transfectants of CM and NES2Y cells. TRAIL-induced apoptosis and cytotoxicity to the FADD-DN transfectants were decreased in comparison to those responses in controls (CM, p < 0.01 and p < 0.01; NES2Y, p < 0.05, and p < 0.02, respectively). When CM, NES2Y, and primary islet cells were transfected by AdIkappaB(SA)2, TRAIL-induced IkappaB degradation and nuclear translocation of NF-kappaB p50/p65 were blocked. TRAIL-induced apoptosis and cytotoxicity to AdIkappaB(SA)2 transfectants of these cells were also reduced (CM, p < 0.02 and p < 0.02; NES2Y, p < 0.01 and p < 0.01, respectively, and islet p < 0.01 for cytotoxicity). Finally, cytotoxicity induced by TRAIL in CM and NES2Y cells transfected with both FADD-DN and AdIkappaB(SA)2 was reduced, compared with that observed in these cells transfected with either FADD-DN alone or AdIkappaB(SA)2 alone, suggesting that FADD and NF-kappaB have synergistic proapoptotic regulatory effects on the susceptibility of beta cell lines and islet cells to TRAIL-induced destruction.

Authors+Show Affiliations

Department of Pediatrics, Faculty of Medicine, University of British Columbia, BC, Vancouver, Canada. daweiou@interchange.ubc.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16112027

Citation

Ou, D, et al. "Regulation of TNF-related Apoptosis-inducing Ligand-mediated Death-signal Pathway in Human Beta Cells By Fas-associated Death Domain and Nuclear Factor KappaB." Human Immunology, vol. 66, no. 7, 2005, pp. 799-809.
Ou D, Wang X, Metzger DL, et al. Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway in human beta cells by Fas-associated death domain and nuclear factor kappaB. Hum Immunol. 2005;66(7):799-809.
Ou, D., Wang, X., Metzger, D. L., Robbins, M., Huang, J., Jobin, C., Chantler, J. K., James, R. F., Pozzilli, P., & Tingle, A. J. (2005). Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway in human beta cells by Fas-associated death domain and nuclear factor kappaB. Human Immunology, 66(7), 799-809.
Ou D, et al. Regulation of TNF-related Apoptosis-inducing Ligand-mediated Death-signal Pathway in Human Beta Cells By Fas-associated Death Domain and Nuclear Factor KappaB. Hum Immunol. 2005;66(7):799-809. PubMed PMID: 16112027.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway in human beta cells by Fas-associated death domain and nuclear factor kappaB. AU - Ou,D, AU - Wang,X, AU - Metzger,D L, AU - Robbins,M, AU - Huang,J, AU - Jobin,C, AU - Chantler,J K, AU - James,R F L, AU - Pozzilli,P, AU - Tingle,A J, PY - 2005/01/29/received PY - 2005/03/21/revised PY - 2005/03/25/accepted PY - 2005/8/23/pubmed PY - 2005/12/13/medline PY - 2005/8/23/entrez SP - 799 EP - 809 JF - Human immunology JO - Hum Immunol VL - 66 IS - 7 N2 - Transfectants of human CM and NES2Y beta cell lines and primary islets transfected by FADD-DN (dominant-negative form of Fas-associated death domain), a mutant of FADD and/or a superrepressor of nuclear factor kappaB (NF-kappaB) (AdIkappaB(SA)2), were examined for their susceptibility to the TRAIL (TNF-related apoptosis-inducing ligand)-induced death signal pathway, compared with controls, wild-type cells, and vector transfectants in caspase fluorescence, Western blot, electrophoretic mobility shift, apoptosis, and cytotoxicity assays. FADD-DN inhibited caspase-8 activation induced by TRAIL in the transfectants of CM and NES2Y cells. TRAIL-induced apoptosis and cytotoxicity to the FADD-DN transfectants were decreased in comparison to those responses in controls (CM, p < 0.01 and p < 0.01; NES2Y, p < 0.05, and p < 0.02, respectively). When CM, NES2Y, and primary islet cells were transfected by AdIkappaB(SA)2, TRAIL-induced IkappaB degradation and nuclear translocation of NF-kappaB p50/p65 were blocked. TRAIL-induced apoptosis and cytotoxicity to AdIkappaB(SA)2 transfectants of these cells were also reduced (CM, p < 0.02 and p < 0.02; NES2Y, p < 0.01 and p < 0.01, respectively, and islet p < 0.01 for cytotoxicity). Finally, cytotoxicity induced by TRAIL in CM and NES2Y cells transfected with both FADD-DN and AdIkappaB(SA)2 was reduced, compared with that observed in these cells transfected with either FADD-DN alone or AdIkappaB(SA)2 alone, suggesting that FADD and NF-kappaB have synergistic proapoptotic regulatory effects on the susceptibility of beta cell lines and islet cells to TRAIL-induced destruction. SN - 0198-8859 UR - https://www.unboundmedicine.com/medline/citation/16112027/Regulation_of_TNF_related_apoptosis_inducing_ligand_mediated_death_signal_pathway_in_human_beta_cells_by_Fas_associated_death_domain_and_nuclear_factor_kappaB_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0198-8859(05)00071-6 DB - PRIME DP - Unbound Medicine ER -