Specific palindromic sequences in synthetic oligonucleotides are required to induce IFN and augment IFN-mediated natural killer activity. To study the mechanism of IFN induction by oligonucleotides containing palindromic sequences, we investigated the possible target molecules of the oligonucleotides. Oligo-1, a 30mer single-stranded oligonucleotide with oligoG sequences next to the active palindromic sequence (AACGTT), had more activity than oligonucleotides with oligoA, oligoC, or oligoT sequences. The activity of oligo-1 was inhibited by a guanine homo-oligomer (G30), dextran sulfate, and polyvinyl sulfate. Oligo-1 bound to plastic-adherent mouse splenocytes, and the binding was inhibited by G30, dextran sulfate, and polyvinyl sulfate. Oligo-1 inhibited acetyl-LDL binding to the scavenger receptor on mouse splenocytes. These findings suggest that the binding of an extrapalindromic sequence to the scavenger receptor is required for the immunostimulatory activity of oligo-1.
Based on the previous finding that certain 30‐mer single‐stranded oligodeoxyribonucleotides (oligonucleotides) having particular 6‐mer palindromic sequences could induce interferon‐alpha and ‐gamma, and enhance natural killer activity, the present study was carried out to clarify the entire relationship between the activity and the sequence of 30‐mer oligonucleotides. The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5 ‐CG‐3 motif(s). The size and the number of palindromes as well as the extra‐palindromic sequences also influenced the activity. An oligonucleotide with a 10‐mer palindrome and extra‐palindromic oligoguanylate sequences showed the strongest activity among the oligonucleotides tested.
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