title: Inhibition of skin inflammation and atopic dermatitis by topical application of a novel ceramide derivative, K112PC-5, in mice.
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.
authors.affiliation: Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Korea.
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Han
authors.forename: Hyunju
authors.initials: H
authors.lastname: Lee
authors.forename: Jong-Kyung
authors.initials: JK
authors.lastname: Youm
authors.forename: Se Kyoo
authors.initials: SK
authors.lastname: Jeong
authors.forename: Byeong Deog
authors.initials: BD
authors.lastname: Park
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000287:Administration, Topical; D000485:Allergens / Q000633:toxicity; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000008:administration & dosage / Q000494:pharmacology*; D003876:Dermatitis, Atopic / Q000473:pathology / Q000517:prevention & control*; D003877:Dermatitis, Contact / Q000473:pathology / Q000517:prevention & control*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004431:Ear, External / Q000473:pathology; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D039981:Pyroglyphidae; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000485:Allergens; D002518:Ceramides; D003879:Dermatologic Agents; D007375:Interleukin-1; C532263:K112PC-5 compound; D015847:Interleukin-4; D009569:Nitric Oxide; D013755:Tetradecanoylphorbol Acetate