Antisense Phosphorothioate Oligonucleotide Inhibits Interleukin 1β Production in the Human Macrophage-Like Cell Line,U937

Abstract

To find more efficacious therapeutic possibilities for treatment of inflammatory disease, we studied the effects of antisense oligonucleotides on interleukin 1β (IL-1β) production of the human macrophage-like U937 cells. U937 cells were incubated with several kinds of oligonucleotides. Total human IL-1β production was determined using an enzyme-linked immunosorbent assay. An antisense phosphorothioate oligonucleotide (S-oligo), complementary to the sequence, including initiation codon of the IL-1β gene, inhibited IL-1β production in a dose-dependent and sequence-specific manner. The effect of the antisense S-oligo was neutralized by mixing with a sense but not with a scramble S-oligo. Cellular uptake of S-oligo scanned with a laser confocal imaging system was time and temperature dependent, and its intracellular distribution was mainly to the cytosols in U937 cells. Human IL-1β antisense S-oligo inhibited IL-1β production of U937 cells, suggesting a potential to reduce some kinds of inflammatory processes.