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Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: Structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges

Authors
 Mao-Qiang Man  ;  Yutaka Hatano  ;  Seung H. Lee  ;  Mona Man  ;  Sandra Chang  ;  Kenneth R. Feingold  ;  Donald Y.M. Leung  ;  Walter Holleran  ;  Yoshikazu Uchida  ;  Peter M. Elias 
Citation
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.128(1) : 79-86, 2008 
Journal Title
 JOURNAL OF INVESTIGATIVE DERMATOLOGY 
ISSN
 0022-202X 
Issue Date
2008
MeSH
Animals ; Antimicrobial Cationic Peptides/analysis ; Cathelicidins ; Ceramides/analysis ; DNA-Binding Proteins/analysis ; Dermatitis, Atopic/immunology* ; Dermatitis, Atopic/metabolism ; Disease Models, Animal ; Female ; Haptens/administration & dosage* ; Haptens/immunology ; Immunity, Innate/drug effects ; Immunoglobulin E/blood ; Lipids/analysis ; Mice ; Mice, Hairless ; Oxazolone/administration & dosage* ; Oxazolone/immunology ; Permeability ; Serine Endopeptidases/metabolism ; Th2 Cells/immunology ; Transcription Factors/analysis
Keywords
Animals ; Antimicrobial Cationic Peptides/analysis ; Cathelicidins ; Ceramides/analysis ; DNA-Binding Proteins/analysis ; Dermatitis, Atopic/immunology* ; Dermatitis, Atopic/metabolism ; Disease Models, Animal ; Female ; Haptens/administration & dosage* ; Haptens/immunology ; Immunity, Innate/drug effects ; Immunoglobulin E/blood ; Lipids/analysis ; Mice ; Mice, Hairless ; Oxazolone/administration & dosage* ; Oxazolone/immunology ; Permeability ; Serine Endopeptidases/metabolism ; Th2 Cells/immunology ; Transcription Factors/analysis
Abstract
Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureus colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9-10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.
Files in This Item:
T200801128.pdf Download
DOI
10.1038/sj.jid.5701011
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Seung Hun(이승헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107405
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