title: Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly begins in childhood. K6PC-9p (N-(Ethyl dihydrogenphosphate)-2-hexyl-3-oxo-decanamide) is a synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3-oxo-staramide), which was known to be effective in atopic patients. In this study, we examined the effect of topical application of K6PC-9p on skin inflammation and AD-like skin lesions in mouse models. K6PC-9p dose-dependently inhibited phorbol ester-induced increase in ear thickness in BALB/c mice. Moreover, topical application of K6PC-9p suppressed dust mite extract-induced AD-like skin lesions in NC/Nga mice. Histopathological analysis revealed that both ear swelling and leucocyte infiltration were suppressed by K6PC-9p treatment. K6PC-9p also suppressed IL-4 and TNF-alpha expression in the ears and mast cell infiltration into the ears in NC/Nga mice. Further study demonstrated that K6PC-9p inhibited ConA-induced IL-4 secretion and LPS-induced macrophage activation. Taken together, our results showed that topical application of K6PC-9p exerts beneficial effects in animal model of skin inflammation and AD, suggesting that K6PC-9p might be a promising topical agent for the treatment of inflammatory skin diseases.
authors: Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Korea.
authors: Jong Soon
authors: JS
authors: Kang
authors: Won Kee
authors: WK
authors: Yoon
authors: Jong-Kyung
authors: JK
authors: Youm
authors: Se Kyoo
authors: SK
authors: Jeong
authors: Byeong Deog
authors: BD
authors: Park
authors: Mi Hwa
authors: MH
authors: Han
authors: Hyunju
authors: H
authors: Lee
authors: Eun-Yi
authors: EY
authors: Moon
authors: Sang-Bae
authors: SB
authors: Han
authors: Chang Woo
authors: CW
authors: Lee
authors: Kiho
authors: K
authors: Lee
authors: Song-Kyu
authors: SK
authors: Park
authors: Kyu-Hwan
authors: KH
authors: Yang
authors: Hwan Mook
authors: HM
authors: Kim
mesh_terms: D000287:Administration, Topical; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000737:chemistry / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000473:pathology / Q000517:prevention & control*; D003877:Dermatitis, Contact / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004431:Ear, External / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D002518:Ceramides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone