Dajee Maya, Muchamuel Tony, Schryver Brian, Oo Aung, Alleman-Sposeto Jennifer, De Vry Christopher G, Prasad Srinivasa, Ruhrmund Donald, Shyamsundar Radha, Mutnick Debra, Mai Kim, Le Tina, Parham Christi, Zhang Jie, Komuves Laszlo, Colby Timothy, Hudak Susan, McEvoy Leslie M, Ehrhardt Rolf O
Department of Research, Corgentech. Inc., South San Francisco, California, USA.
J Invest Dermatol. 2006 Aug;126(8):1792-803. doi: 10.1038/sj.jid.5700307. Epub 2006 Apr 20.
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-kappaB transcription factor family plays a central role in the progression and maintenance of AD. This study explores the possibility of using topical NF-kappaB Decoy as a novel therapeutic alternative for targeting Th1/Th2-driven skin inflammation in experimental AD. A high-affinity, topical NF-kappaB Decoy developed for human efficacy demonstrates: (i) efficient NF-kappaB Decoy penetration in pig skin, (ii) NF-kappaB 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-kappaB 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-kappaB Decoy treatment does not induce skin atrophy. Moreover, topical NF-kappaB Decoy, in contrast to BMV, restores compromised stratum corneum integrity and barrier function. Steroid withdrawal causes rapid rebound of inflammation, while the NF-kappaB Decoy therapeutic benefit was maintained for weeks. Thus, topical NF-kappaB Decoy provides a novel mechanism of reducing chronic skin inflammation with improved skin homeostasis and minimal side effects.
特应性皮炎（AD）是一种常见的慢性皮肤炎症性疾病。在皮肤炎症中长期使用外用皮质类固醇会带来全身和局部副作用的风险。核因子-κB（NF-κB）转录因子家族在AD的进展和维持中起核心作用。本研究探讨了使用外用NF-κB诱饵作为一种新型治疗方法来靶向实验性AD中由Th1/Th2驱动的皮肤炎症的可能性。一种为人体疗效开发的高亲和力外用NF-κB诱饵显示：（i）在猪皮肤中有效渗透，（ii）在角质形成细胞和关键免疫细胞中核定位，以及（iii）在慢性尘螨抗原皮肤炎症治疗模型中具有强大的“类固醇样”疗效。NF-κB诱饵通过有效抑制炎症的关键调节因子和诱导关键免疫细胞凋亡来发挥其抗炎作用。与戊酸倍他米松（BMV）不同，长期使用NF-κB诱饵治疗不会导致皮肤萎缩。此外，与BMV相比，外用NF-κB诱饵可恢复受损的角质层完整性和屏障功能。停用类固醇会导致炎症迅速反弹，而NF-κB诱饵的治疗益处可维持数周。因此，外用NF-κB诱饵提供了一种减少慢性皮肤炎症的新机制，可改善皮肤内环境稳定并使副作用最小化。
