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

The Journal of Investigative Dermatology
Maya DajeeRolf O Ehrhardt

Abstract

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, whil...Continue Reading

References

Dec 1, 1990·The Journal of Clinical Investigation·T S Kupper
Jan 1, 1981·Springer Seminars in Immunopathology·D Y Leung, R S Geha
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C K JiangM Blumenberg
Mar 1, 1996·American Journal of Respiratory and Critical Care Medicine·P AutioA Oikarinen
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·V J DzauY Kaneda
Oct 1, 1996·The British Journal of Dermatology·A Y Finlay
Oct 1, 1996·Archives of Dermatological Research·M LeP G van der Valk
Jan 13, 1998·Current Opinion in Pediatrics·D Y Leung
Mar 7, 2001·The Journal of Investigative Dermatology·J S KaoP M Elias
Jan 5, 2002·Seminars in Cutaneous Medicine and Surgery·M Boguniewicz, D Y Leung
Feb 28, 2002·Trends in Immunology·Khusru AsadullahAndrew C B Cato
Nov 21, 2002·Pharmacology & Therapeutics·Heike SchäckeKhusru Asadullah
Nov 22, 2002·Dermatology : International Journal for Clinical and Investigative Dermatology·Katsuko Kikuchi, Hachiro Tagami
Jun 4, 2004·The Journal of Investigative Dermatology·Jens-Michael JensenEhrhardt Proksch
Jun 4, 2004·Current Allergy and Asthma Reports·Natalija NovakStefan Kraft
Aug 23, 2005·Dermatologic Clinics·Dónal G FortuneChristopher E M Griffiths

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Citations

Feb 17, 2009·Expert Opinion on Emerging Drugs·Peck Y Ong
Nov 26, 2015·Expert Opinion on Drug Delivery·Ibrahim A AljuffaliJia-You Fang
Nov 6, 2007·The Journal of Allergy and Clinical Immunology·Andreas H WagnerMarkus Hecker
Feb 25, 2010·Veterinary Dermatology·Maja M SuterEliane J Müller
Dec 24, 2013·Journal of Dermatological Science·Knut SchäkelIna Bosselmann
Oct 9, 2007·Journal of Neuroscience Research·Danny Salah RafatiJ Regino Perez-Polo
Dec 16, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yatrik M ShahFrank J Gonzalez
Dec 4, 2019·The British Journal of Dermatology·A J HendricksV Y Shi
Jun 24, 2020·International Journal of Immunopathology and Pharmacology·Chieh-Shan WuChi-Chien Lin
Jan 12, 2019·Frontiers in Immunology·Debajyoti GhoshTesfaye B Mersha
May 3, 2011·The Journal of Pharmacology and Experimental Therapeutics·Tamae UchidaHiroaki Okada
Dec 3, 2014·The Journal of Allergy and Clinical Immunology·Mei MingYu-Ying He
Jan 14, 2020·The Journal of Allergy and Clinical Immunology·Yong Sun LeeJin Tae Hong
May 28, 2015·The Journal of Allergy and Clinical Immunology·Giulia FornasaMaria Rescigno
Jul 17, 2021·The Journal of Allergy and Clinical Immunology·Stanley B DeVoreGurjit K Khurana Hershey

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