Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice.
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.
Kang
Jong Soon
JS
Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Korea.
Yoon
Won Kee
WK
Youm
Jong-Kyung
JK
Jeong
Se Kyoo
SK
Park
Byeong Deog
BD
Han
Mi Hwa
MH
Lee
Hyunju
H
Moon
Eun-Yi
EY
Han
Sang-Bae
SB
Lee
Chang Woo
CW
Lee
Kiho
K
Park
Song-Kyu
SK
Yang
Kyu-Hwan
KH
Kim
Hwan Mook
HM
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
D039741:Antigens, Dermatophagoides; D002518:Ceramides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone