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Pseudoceramide stimulates peroxisome proliferator-activated receptor-α expression in a murine model of atopic dermatitis: molecular basis underlying the anti-inflammatory effect and the preventive effect against steroid-induced barrier impairment

Authors
 Sang Eun Lee  ;  Min Kyung Jung  ;  Seung Joon Oh  ;  Se Kyoo Jeong  ;  Seung Hun Lee 
Citation
 ARCHIVES OF DERMATOLOGICAL RESEARCH, Vol.307(9) : 781-792, 2015 
Journal Title
 ARCHIVES OF DERMATOLOGICAL RESEARCH 
ISSN
 0340-3696 
Issue Date
2015
MeSH
Administration, Topical ; Animals ; Anti-Inflammatory Agents/therapeutic use* ; Arachidonic Acids/therapeutic use* ; Ceramides/therapeutic use* ; Dermatitis, Atopic/drug therapy* ; Dermatitis, Atopic/pathology ; Female ; Glucocorticoids/adverse effects ; Inflammation ; Membrane Proteins/biosynthesis ; Mice ; Mice, Hairless ; Oxazolone/pharmacology ; PPAR alpha/antagonists & inhibitors ; PPAR alpha/biosynthesis* ; Skin/metabolism ; Skin/pathology ; Stearic Acids/therapeutic use* ; Tight Junctions/drug effects*
Keywords
Atopic dermatitis ; Glucocorticoid ; Peroxisome proliferator-activated receptor-α ; Pseudoceramide
Abstract
Topical pseudoceramides are successfully used in skin barrier repair therapy for atopic dermatitis (AD) and demonstrated to reduce the adverse effects of topical glucocorticoids (GC). However, the molecular mechanisms involved are not fully understood. We investigated whether PC-9S (myristoyl/palmitoyloxostearamide/arachamide MEA, Neopharm, Daejeon, Korea), one of the synthetic pseudoceramides, could stimulate peroxisome proliferator-activated receptor (PPAR)α expression in a hapten [oxazolone (oxa)]-induced AD murine model (oxa-AD mice) and subsequently improved permeability barrier, reduced inflammation, and increased antimicrobial peptides (AMPs) expression. Normal hairless mice and oxa-AD mice were topically treated twice daily with either PC-9S-containing physiologic lipid mixture (PLM), vehicle (PLM), or PPARα agonist for 4 days. Topical PC-9S significantly increased PPARα expression in mouse epidermis in vivo and in oxa-AD mice skin comparable with PPARα agonist. Topical PC-9S-containing PLM significantly reduced basal trans-epidermal water loss (TEWL), surface pH, and mast cell infiltrates and prevented the decline of AMPs expression in oxa-AD mice, which were abrogated by PPARα antagonist. Then, oxa-AD mice were treated with super-potent topical GC twice daily for 4 days with or without PC-9S co-applications. Co-treatment with PC-9S-containing PLM suppressed GC-induced increase in basal TEWL, epidermal thinning, reduced loricrin expression, and impaired barrier recovery and these effects were attenuated by PPARα antagonist. Collectively, our findings suggest that pseudoceramide PC-9S-induced stimulation of PPARα expression provides a new mechanism by which pseudoceramides show anti-inflammatory property, improve the permeability and antimicrobial barrier function, and prevent the negative effects of topical GC.
Full Text
http://link.springer.com/article/10.1007%2Fs00403-015-1584-9
DOI
10.1007/s00403-015-1584-9
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sang Eun(이상은) ORCID logo https://orcid.org/0000-0003-4720-9955
Lee, Seung Hun(이승헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141758
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