title: Interleukin-1beta mediates LPS-induced inhibition of apoptosis in retinoic acid-differentiated HL-60 cells.
abstract: Promyelocytic HL-60 cells differentiated to a neutrophilic phenotype by incubation with all-trans retinoic acid become constitutively apoptotic. Exposure to either LPS or IL-1beta inhibited the apoptosis of differentiated HL-60 cells. LPS induced the expression of pro-IL-1beta message, upregulated the activity of the interleukin-1beta converting enzyme (caspase-1), and increased the release of IL-1beta into the culture medium. Prevention of IL-1beta translation with an anti-sense oligonucleotide, or prevention of IL-1beta cellular binding with a blocking antibody, accelerated rates of spontaneous apoptosis, and abrogated the inhibitory effects of LPS. However inhibition of caspase-1 activity further inhibited constitutive apoptosis of mature HL-60 cells. These studies provide further evidence of a complex regulatory pathway that modulates the expression of granulocyte apoptosis during inflammation, and point to a specific role for IL-1beta as an autocrine survival factor.
authors.affiliation: Department of Surgery, St. Michael's Hospital, University of Toronto, 4th Floor Bond Wing, Room 4-007, 30 Bond Street, Toronto, Ont., Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Song Hui
authors.initials: SH
authors.lastname: Jia
authors.forename: Jean
authors.initials: J
authors.lastname: Parodo
authors.forename: R William G
authors.initials: RW
authors.lastname: Watson
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018922:HL-60 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014212:Tretinoin