Interleukin-1β mediates LPS-induced inhibition of apoptosis in retinoic acid-differentiated HL-60 cells

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-1β inhibited the apoptosis of differentiated HL-60 cells. LPS induced the expression of pro-IL-1β message, upregulated the activity of the interleukin-1β converting enzyme (caspase-1), and increased the release of IL-1β into the culture medium. Prevention of IL-1β translation with an anti-sense oligonucleotide, or prevention of IL-1β 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-1β as an autocrine survival factor.