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Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice.

Tanaka A, Muto S, Jung K, Itai A, Matsuda H

Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Growing evidence has demonstrated the crucial role of NF-kappaB activation on disease severity in allergic disorders. In this study, we examined the clinical relevance of a novel NF-kappaB inhibitor, IMD-0354, for atopic dermatitis (AD) by its topical application. To investigate the in vivo efficacy, 1% IMD-0354 ointment was applied daily to NC/NgaTnd mice with severe dermatitis, which served as a model for human AD. During 2 weeks of treatment, scratching behavior decreased and severity of dermatitis reduced in mice treated with IMD-0354 as well as FK506 without diverse effects. Based on histological examinations, the hyperplasia of keratinocytes and infiltration of inflammatory cells were significantly reduced in the skin of IMD-0354-treated mice. The expressions of T-helper 2 cytokines and tumor necrosis factor-alpha at the affected skin sites were downregulated in IMD-0354-treated mice. Furthermore, IMD-0354 suppressed the proliferation of various immunocompetent cells, neurite outgrowth of nerve growth factor-stimulated pheochromocytoma cells, IgE production from splenic B cells, and IgE-mediated activation of mast cells in vitro. IMD-0354 effectively reduced the allergic inflammation in NC/NgaTnd mice in vivo. Thus, a drug that interferes with NF-kappaB activity may provide an alternative therapeutic strategy for the treatment of AD.

Published 16 March 2007 in J Invest Dermatol, 127(4): 855-63.
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