Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice.
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.
Sakamoto
T
T
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo, Japan.
Miyazaki
E
E
Aramaki
Y
Y
Arima
H
H
Takahashi
M
M
Kato
Y
Y
Koga
M
M
Tsuchiya
S
S
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D007073:Immunoglobulin E / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000276:immunology; D012869:Skin Absorption
D016207:Cytokines; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016753:Interleukin-10; D007073:Immunoglobulin E