KMID : 0043320080310081004
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Archives of Pharmacal Research 2008 Volume.31 No. 8 p.1004 ~ p.1009
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Inhibition of Skin Inflammation and Atopic Dermatitis by Topical Application of a Novel Ceramide Derivative, K112PC-5, in Mice
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Kang Jong-Soon
Youm Jong-Kyung Park Byeong-Deog Han Sang-Bae Lee Chang-Woo Jeong Se-Kyoo Kim Hwan-Mook Park Song-Kyu Han Gyoon-Hee Lee Ki-Ho Han Mi-Hwa Lee Hyun-Ju
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Abstract
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PC-9S (N-Ethanol-2-mirystyl-3-oxo-stearamide) is a synthetic ceramide and has been known to be effective in atopic and psoriatic patients. K112PC-5 (2-Acetyl-N-(1,3-dihydroxyisopropyl)-tetradecanamide) is a novel ceramide derivative of PC-9S. In the present study, we examined the effect of K112PC-5 on macrophage and T lymphocyte function in primary macrophages and splenocytes, respectively, as well as the effect of topical application of K112PC-5 on skin inflammation and atopic dermatitis (AD) in mouse models. K112PC-5 inhibited lipopolysaccharide-induced nitrite generation in mouse peritoneal macrophages in a dose-dependent manner. However, K112PC-5 did not affect concanavalin A-induced proliferation, interleukin (IL)-2 secretion and IL-4 secretion in mouse splenocytes. In addition, K112PC-5 significantly suppressed the increase in phorbol ester-induced ear thickness in BALB/c mice. Further study demonstrated that topical application of K112PC-5 also inhibited AD induced by extracts of dust mites, Dermatophagoides pteronyssinus and Dermatophagoides farinae, in NC/Nga mice. Taken together, these results showed that K112PC-5 exerted an anti-inflammatory effect both in vitro and in vivo and proved to be beneficial in an animal model of AD. Our results suggest that K112PC-5 might be beneficial as a topical agent for the treatment of AD.
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KEYWORD
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K112PC-5, Macrophage, Skin inflammation, Atopic dermatitis, Dust mite, NC/Nga
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