Inhibition of skin inflammation and atopic dermatitis by topical application of a novel ceramide derivative, K112PC-5, in mice

Jong Soon Kang, Chang Woo Lee, Kiho Lee, Mi Hwa Han, Hyunju Lee, Jong Kyung Youm, Se Kyoo Jeong, Byeong Deog Park, Sang Bae Han, Gyoonhee Han, Song Kyu Park, Hwan Mook Kim

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Abstract

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.

Original languageEnglish
Pages (from-to)1004-1009
Number of pages6
JournalArchives of pharmacal research
Volume31
Issue number8
DOIs
Publication statusPublished - 2008 Aug

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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    Kang, J. S., Lee, C. W., Lee, K., Han, M. H., Lee, H., Youm, J. K., Jeong, S. K., Park, B. D., Han, S. B., Han, G., Park, S. K., & Kim, H. M. (2008). Inhibition of skin inflammation and atopic dermatitis by topical application of a novel ceramide derivative, K112PC-5, in mice. Archives of pharmacal research, 31(8), 1004-1009. https://doi.org/10.1007/s12272-001-1260-z