Ding M, Zhang M, Wong J L, Voskuhl R R, Ellison G W
Department of Neurology, School of Medicine, University of California at Los Angeles, Reed Neurological Research Center 90095-1769, USA.
Neurosci Lett. 1996 Dec 13;220(2):89-92. doi: 10.1016/s0304-3940(96)13229-8.
Increasing evidence suggests a correlation between cytokine-induced nitric oxide synthase (iNOS) and demyelination in Multiple sclerosis (MS). Inhibition of iNOS may therefore be a novel therapeutic approach in MS. To test an antisense oligodeoxynucleotide (ODN) knockdown strategy for inhibiting iNOS, we used lipopolysaccharide (LPS) together with gamma-interferon (IFN-gamma) to induce iNOS in adult mouse mixed glial cell cultures. We administered an iNOS-derived antisense phosphorothiorate oligodeoxynucleotide (S-ODN) to block the induction. The antisense ODN treatment resulted in significant inhibition of LPS and IFN-gamma induced iNOS mRNA and protein expression. It also inhibited nitric oxide (NO) and cyclic GMP (cGMP) production in a dose dependent fashion. Sense and random S-oligo had no effect in any of these studies. These data indicate the efficacy and specificity of the antisense oligodeoxynucleotide approach in inhibiting iNOS in glial cells.
越来越多的证据表明，细胞因子诱导型一氧化氮合酶（iNOS）与多发性硬化症（MS）的脱髓鞘之间存在关联。因此，抑制iNOS可能是MS的一种新型治疗方法。为了测试用于抑制iNOS的反义寡脱氧核苷酸（ODN）敲低策略，我们使用脂多糖（LPS）与γ-干扰素（IFN-γ）一起在成年小鼠混合神经胶质细胞培养物中诱导iNOS。我们给予一种源自iNOS的反义硫代磷酸酯寡脱氧核苷酸（S-ODN）以阻断诱导。反义ODN处理导致LPS和IFN-γ诱导的iNOS mRNA和蛋白质表达受到显著抑制。它还以剂量依赖性方式抑制一氧化氮（NO）和环磷酸鸟苷（cGMP）的产生。正义和随机S-寡核苷酸在任何这些研究中均无作用。这些数据表明反义寡脱氧核苷酸方法在抑制神经胶质细胞中iNOS方面的有效性和特异性。
