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NF-κB诱骗寡核苷酸增强紫外线诱导的细胞凋亡

Enhancement of ultraviolet-induced apoptosis by NF-kappaB decoy oligonucleotides.

作者信息

Yokoyama S, Nakano H, Yamazaki T, Tamai K, Hanada K, Takahashi G

机构信息

Department of Dermatology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.

出版信息

Br J Dermatol. 2005 Dec;153 Suppl 2:47-51. doi: 10.1111/j.1365-2133.2005.06969.x.

Abstract

BACKGROUND

A decoy strategy utilizing oligonucleotides (ODN) containing the specific binding sequence of a certain transcription factor has been developed and is considered to be a potential new class of antigene therapy. However, the application of this new therapeutic modality to skin diseases has not been fully documented.

OBJECTIVES

The aim of this work was to examine the effects of the nuclear factor (NF)-kappaB decoy ODN on UV-elicited skin change.

METHODS

Mouse keratinocyte Pam 212 cells were transfected with NF-kappaB decoy ODN to examine the effects of the decoy ODN on ultraviolet (UV) B-induced apoptosis. Tape-stripped rat dorsal skin was treated with an ointment containing NF-kappaB decoy ODN for the examination of the in vivo impact of the decoy ODN on sunburned cell (SBC) formation and UVB erythema.

RESULTS

NF-kappaB decoy ODN specifically induced apoptosis of Pam 212 cells and SBC formation was significantly enhanced by topical NF-kappaB decoy ODN ointment, while UV-induced erythema was not affected.

CONCLUSIONS

These data suggest that enhancement of UV-induced apoptosis by NF-kappaB decoy ODN may play a cancer-preventive role by further eliminating photodamaged keratinocytes.

摘要

背景

一种利用含有特定转录因子结合序列的寡核苷酸(ODN)的诱饵策略已被开发出来,并被认为是一类潜在的新型抗原治疗方法。然而,这种新的治疗方式在皮肤病中的应用尚未得到充分记录。

目的

本研究旨在探讨核因子(NF)-κB诱饵ODN对紫外线引起的皮肤变化的影响。

方法

用NF-κB诱饵ODN转染小鼠角质形成细胞Pam 212,以研究诱饵ODN对紫外线(UV)B诱导的细胞凋亡的影响。用含NF-κB诱饵ODN的软膏处理胶带剥离的大鼠背部皮肤,以研究诱饵ODN对晒伤细胞(SBC)形成和UVB红斑的体内影响。

结果

NF-κB诱饵ODN特异性诱导Pam 212细胞凋亡,局部应用NF-κB诱饵ODN软膏可显著增强SBC形成,而UV诱导的红斑不受影响。

结论

这些数据表明,NF-κB诱饵ODN增强UV诱导的细胞凋亡可能通过进一步清除光损伤的角质形成细胞而发挥癌症预防作用。

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