ANTISENSE PHOSPHOROTHIOATE OLIGONUCLEOTIDE INHIBITS INTERLEUKIN-1-BETA PRODUCTION IN THE HUMAN MACROPHAGE-LIKE CELL-LINE, U937

To find more efficacious therapeutic possibilities for treatment of in flammatory disease, we studied the effects of antisense oligonucleotid es on interleukin 1 beta (IL-1 beta) production of the human macrophag e-like U937 cells, U937 cells were incubated with several kinds of oli gonucleotides, Total human IL-1 beta production was determined using a n enzyme-linked immunosorbent assay, An antisense phosphorothioate oli gonucleotide (S-oligo), complementary to the sequence, including initi ation codon of the IL-1 beta gene, inhibited IL-1 beta production in a dose-dependent and sequence-specific manner, The effect of the antise nse S-oligo was neutralized by mixing with a sense but not with a scra mble S-oligo, Cellular uptake of S-oligo scanned with a laser confocal imaging system was time and temperature dependent, and its intracellu lar distribution was mainly to the cytosols in U937 cells, Human IL-1 beta antisense S-oligo inhibited IL-1 beta production of U937 cells, s uggesting a potential to reduce some kinds of inflammatory processes.