Antisense phosphorothioate oligonucleotide inhibits interleukin 1 beta production in the human macrophage-like cell line, U937.

Antisense & nucleic acid drug development

PubMedID: 8783796

Yahata N, Kawai S, Higaki M, Mizushima Y. Antisense phosphorothioate oligonucleotide inhibits interleukin 1 beta production in the human macrophage-like cell line, U937. Antisense Nucleic Acid Drug Dev. 1997;6(1):55-61.
To find more efficacious therapeutic possibilities for treatment of inflammatory disease, we studied the effects of antisense oligonucleotides on interleukin 1 beta (IL-1 beta) production of the human macrophage-like U937 cells. U937 cells were incubated with several kinds of oligonucleotides. Total human IL-1 beta 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-1 beta gene, inhibited IL-1 beta 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-1 beta antisense S-oligo inhibited IL-1 beta production of U937 cells, suggesting a potential to reduce some kinds of inflammatory processes.