Blockade of experimental atopic dermatitis via topical NF-κB decoy oligonucleotide

被引：43

作者：

Dajee, Maya ^{[1
]}

Muchamuel, Tony ^{[1
]}

Schryver, Brian ^{[1
]}

Oo, Aung ^{[1
]}

Alleman-Sposeto, Jennifer ^{[1
]}

De Vry, Christopher G. ^{[1
]}

Prasad, Srinivasa ^{[1
]}

Ruhrmund, Donald ^{[1
]}

Shyamsundar, Radha ^{[1
]}

Mutnick, Debra ^{[1
]}

Mai, Kim ^{[1
]}

Le, Tina ^{[1
]}

Parham, Christi ^{[1
]}

Zhang, Jie ^{[1
]}

Komuves, Laszlo ^{[1
]}

Colby, Timothy ^{[1
]}

Hudak, Susan ^{[1
]}

McEvoy, Leslie M. ^{[1
]}

Ehrhardt, Rolf O. ^{[1
]}

机构：

[1] Corgentech Inc, Dept Res, San Francisco, CA USA

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2006年 / 126卷 / 08期

关键词：

D O I：

10.1038/sj.jid.5700307

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Atopic dermatitis (AD) is a common chronic skin inflammatory disease. Long-term use of topical corticosteroids in skin inflammation poses risks of systemic and local side effects. The NF-kappa B transcription factor family plays a central role in the progression and maintenance of AD. This study explores the possibility of using topical NF-kappa B Decoy as a novel therapeutic alternative for targeting Th1/Th2-driven skin inflammation in experimental AD. A high-affinity, topical NF-kB Decoy developed for human efficacy demonstrates: (i) efficient NF-kappa B Decoy penetration in pig skin, (ii) NF-kappa B Decoy nuclear localization in keratinocytes and key immune cells, and (iii) potent "steroid-like'' efficacy in a chronic dust-mite antigen skin inflammation treatment model. NF-kappa B Decoy exerts its anti-inflammatory action through the effective inhibition of essential regulators of inflammation and by induction of apoptosis of key immune cells. Unlike betamethasone valerate (BMV), long-term NF-kappa B Decoy treatment does not induce skin atrophy. Moreover, topical NF-kappa B Decoy, in contrast to BMV, restores compromised stratum corneum integrity and barrier function. Steroid withdrawal causes rapid rebound of inflammation, while the NF-kappa B Decoy therapeutic benefit was maintained for weeks. Thus, topical NF-kappa B Decoy provides a novel mechanism of reducing chronic skin inflammation with improved skin homeostasis and minimal side effects.

引用

页码：1792 / 1803

页数：12

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[1] Novel immunotherapies for psoriasis [J].