title: Apoptosis induced by avian H5N1 virus in human monocyte-derived macrophages involves TRAIL-inducing caspase-10 activation.
abstract: Avian influenza virus H5N1 is a potentially fatal disease not only in birds, but also in humans. The virus is able to induce apoptosis in many cell types including macrophages and dendritic cells. In the present study, we demonstrated that TNF-related apoptosis-inducing ligand (TRAIL) is involved in apoptosis-associated mechanisms of apoptosis downstream of the TRAIL receptor in H5N1 virus-infected human monocyte-derived macrophages (MDMs). Activation of caspase-10 was also observed in avian virus H5N1-infected MDMs. In the presence of caspase-10 inhibitor, Z-AEVD-FMK, the activation of Bid and a release of apoptotic-inducing factor (AIF) from mitochondria were markedly reduced, resulting in a significant decrease of apoptotic cells which suggested the involvement of caspase-10 activation in mitochondria leakage. Furthermore, neutralizing Ab against TRAIL significantly reduced caspase-10 activities, which paralleled with a decrease in the number of apoptotic cells. Together, this study demonstrated that apoptosis in avian virus H5N1-infected MDMs was induced by TRAIL-activated caspase-10, resulting in the activation of Bid and the release of AIF from mitochondria.
authors.affiliation: Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Peeraya
authors.initials: P
authors.lastname: Ekchariyawat
authors.forename: Arunee
authors.initials: A
authors.lastname: Thitithanyanont
authors.forename: Stitaya
authors.initials: S
authors.lastname: Sirisinha
authors.forename: Pongsak
authors.initials: P
authors.lastname: Utaisincharoen
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis / Q000235:genetics; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D001717:Birds; D053455:Caspase 10 / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D009842:Oligopeptides / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D009842:Oligopeptides; D053221:TNF-Related Apoptosis-Inducing Ligand; C470795:benzyloxycarbonyl-alanyl-glutamyl-valyl-aspartic acid fluoromethyl ketone; D053455:Caspase 10