Kimura Y, Sonehara K, Kuramoto E, Makino T, Yamamoto S, Yamamoto T, Kataoka T, Tokunaga T
Institute of Biological Science, Mitsui Pharmaceuticals Inc., Chiba.
J Biochem. 1994 Nov;116(5):991-4. doi: 10.1093/oxfordjournals.jbchem.a124658.
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.
合成寡核苷酸中特定的回文序列是诱导干扰素（IFN）并增强IFN介导的自然杀伤活性所必需的。为了研究含回文序列的寡核苷酸诱导IFN的机制，我们研究了寡核苷酸可能的靶分子。Oligo-1是一种30聚体单链寡核苷酸，在活性回文序列（AACGTT）旁边有oligoG序列，其活性比含oligoA、oligoC或oligoT序列的寡核苷酸更强。Oligo-1的活性受到鸟嘌呤同聚物（G30）、硫酸葡聚糖和聚硫酸乙烯酯的抑制。Oligo-1与贴壁的小鼠脾细胞结合，且这种结合受到G30、硫酸葡聚糖和聚硫酸乙烯酯的抑制。Oligo-1抑制乙酰低密度脂蛋白（acetyl-LDL）与小鼠脾细胞上清道夫受体的结合。这些发现表明，oligo-1的免疫刺激活性需要回文外序列与清道夫受体结合。
