Yokozeki Hiroo
Tokyo Medical and Dental University Graduate School, Department of Dermatology.
Nihon Rinsho Meneki Gakkai Kaishi. 2012;35(2):107-11. doi: 10.2177/jsci.35.107.
Atopic dermatitis (AD) is a common, chronically relapsing skin disease. It is very difficult to treat severe type AD by steroid ointment. We therefore hypothesized that synthetic double-stranded DNA with a high affinity for Signal Transducers and Activators of Transcription 6 (STAT6) could be introduced in vivo as a decoy cis elements to bind the transcriptional factor and to block the gene activation of contributing the onset and progression of AD, thus providing effective therapy for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), but not scrambled decoy ODN in the AD model mice, had a significantly inhibitory effect on not only STAT6 binding to nuclei but also on the third phase response. A histological analysis revealed that both edema and the infiltration of eosinophils and degranulated mast cells significantly decreased in STAT6 decoy ODN transfected mice. We herein report the first successful in vivo transfer of STAT6 decoy ODN to reduce the third phase reaction in AD model mice, thereby providing a new therapeutic strategy for atopic dermatitis. We also introduce another NF-kB Decoy Oligodeoxynucleotides therapy or STAT6siRNA therapy for allergic diseases.
特应性皮炎（AD）是一种常见的慢性复发性皮肤病。使用类固醇软膏治疗重度AD非常困难。因此，我们推测，对信号转导和转录激活因子6（STAT6）具有高亲和力的合成双链DNA可以作为诱饵顺式元件引入体内，以结合转录因子并阻断导致AD发病和进展的基因激活，从而为AD提供有效的治疗方法。在AD模型小鼠中，转染STAT6诱饵寡脱氧核苷酸（ODN）而非乱序诱饵ODN进行治疗，不仅对STAT6与细胞核的结合有显著抑制作用，而且对三期反应也有显著抑制作用。组织学分析显示，转染STAT6诱饵ODN的小鼠中水肿以及嗜酸性粒细胞和脱颗粒肥大细胞的浸润均显著减少。我们在此报告首次成功在体内转移STAT6诱饵ODN以减少AD模型小鼠的三期反应，从而为特应性皮炎提供了一种新的治疗策略。我们还介绍了另一种用于过敏性疾病的NF-κB诱饵寡脱氧核苷酸疗法或STAT6 siRNA疗法。
