title: Crosstalk between autophagy and apoptosis in RAW 264.7 macrophages infected with ectromelia orthopoxvirus.
abstract: Several studies have provided evidence that complex relationships between autophagic and apoptotic cell death pathways occur in cancer and virus-infected cells. Previously, we demonstrated that infection of macrophages with Moscow strain of ectromelia virus (ECTV-MOS) induces apoptosis under in vitro and in vivo conditions. Here, we found that autophagy was induced in RAW 264.7 cells during infection with ECTV-MOS. Silencing of beclin 1, an autophagy-related gene, reduced the percentage of late apoptotic cells in virus-infected RAW 264.7 macrophages. Pharmacological modulation of autophagy by wortmannin (inhibitor) or rapamycin (inductor) did not affect or cause increased apoptosis in ECTV-MOS-infected RAW 264.7 cells, respectively. Meantime, blocking apoptosis by a pan-caspase inhibitor, Z-VAD-FMK, increased the formation of autophagosomes in infected macrophages. Taken together, three important points arise from our study. First, autophagy may co-occur with apoptosis in RAW 264.7 cells exposed to ECTV-MOS. Second, at later stages of infection, autophagy may partially participate in the execution of macrophage cell death by enhancing apoptosis. Third, when apoptosis is blocked infected macrophages undergo increased autophagy. Our results provide new information about the relationship between autophagy and apoptosis in ECTV-MOS-infected macrophages.
authors.affiliation: 1 Division of Immunology, Department of Preclinical Sciences, Warsaw University of Life Sciences SGGW (WULS-SGGW) , Warsaw, Poland .
authors.forename: Lech
authors.initials: L
authors.lastname: Martyniszyn
authors.forename: Lidia
authors.initials: L
authors.lastname: Szulc-Dąbrowska
authors.forename: Anna
authors.initials: A
authors.lastname: Boratyńska-Jasińska
authors.forename: Justyna
authors.initials: J
authors.lastname: Struzik
authors.forename: Anna
authors.initials: A
authors.lastname: Winnicka
authors.forename: Marek
authors.initials: M
authors.lastname: Niemiałtowski
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000071186:Beclin-1; D061945:Caspase Inhibitors / Q000494:pharmacology; D002460:Cell Line; D004481:Ectromelia virus / Q000276:immunology* / Q000472:pathogenicity; D004482:Ectromelia, Infectious / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000730:Androstadienes; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D061945:Caspase Inhibitors; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020123:Sirolimus; D000077191:Wortmannin