SPECIFIC-INHIBITION OF INTERLEUKIN-10 PRODUCTION IN MURINE MACROPHAGE-LIKE CELLS BY PHOSPHOROTHIOATE ANTISENSE OLIGONUCLEOTIDES

The effects of phosphorothioate antisense oligonucleotides (AS-S-oligo s) directed against murine interleukin-10 (IL-10) mRNA on IL-10 produc tion in RAW264.7 cells, a murine macrophage-like cell line, when stimu lated by lipopolysaccharide (LPS) were examined. Of the six AS-S-oligo s used, AS-S-oligos directed against the 3'-untranslated region (3'-UT R) of IL-10 mRNA (AS6-S-oligo) showed the strongest inhibitory effect on IL-10 production, and this inhibition was dose and time dependent. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that the antisense effect originated from a specific reduction of target I L-10 mRNA by hybridization with AS6-S-oligo. In addition, AS6-S-oligo did not affect tumor necrosis factor-alpha (TNF-alpha) production in c ells stimulated by LPS, and S-oligos with control sequences did not af fect IL-10 production. These findings suggested that AS6-S-oligo most powerfully inhibited IL-10 production in macrophages by an antisense m echanism.