Research Article
Gene Therapy (2004) 11, 317–324. doi:10.1038/sj.gt.3302171
Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice
T Sakamoto1, E Miyazaki1, Y Aramaki1, H Arima1,3, M Takahashi1, Y Kato2, M Koga2 and S Tsuchiya1
- 1School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo, Japan
- 2Department of Dermatology, Tokyo Medical University, Shinjuku, Shinjuku-ku, Tokyo, Japan
Correspondence: S Tsuchiya, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
3Present address: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Kumamoto, Kumamoto 862-0973, Japan
Received 7 February 2003; Accepted 19 September 2003.
Abstract
IL-10 is overexpressed in skin lesions of atopic dermatitis (AD) patients and believed to be an important factor in the pathogenesis of the disease. Thus the regulation of IL-10 production is a potential solution for immunotherapeutic intervention in AD. We examined the topical delivery of an antisense oligonucleotide for mouse IL-10 (AS6) and the therapeutic effect on the skin lesions of NC/Nga mice, a human AD model. Using an iontophoresis system, about 30% of the applied dose of AS6 penetrated the skin and was distributed in the epidermis and upper dermis. Topically delivered AS6 decreased the levels of mRNA and protein of IL-10 in the lesions of NC/Nga mice, with no effect on IL-4 levels. The dorsal lesions of NC/Nga mice disappeared with repeated topical application of AS6. Topically delivered AS6 showed an inhibitory effect on the production of IL-10 in the skin lesions of NC/Nga mice and had a therapeutic effect on the established dermatitis.
Keywords:
interleukin-10, antisense oligonucleotides, atopic dermatitis, NC/Nga mice, topical
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