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 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.
Yahata
N
N
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Kawai
S
S
Higaki
M
M
Mizushima
Y
Y
D001483:Base Sequence; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008264:Macrophages; D008856:Microscopy, Fluorescence; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology*; D013873:Thionucleotides; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D007375:Interleukin-1; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides