title: Repeated epicutaneous exposures to ovalbumin progressively induce atopic dermatitis-like skin lesions in mice.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a chronic skin disease in which environmental factors play a great role. A widely used murine model for AD has provided a useful tool to study the disease.
  
  
  OBJECTIVE
  The purpose of this study is to investigate kinetically the induction of this AD model and the processes involved in the development of AD due to extrinsic allergen exposures.
  
  
  METHODS
  BALB/c mice were epicutaneously exposed to ovalbumin (OVA) for 3 weeks; each week was separated by a 2-week resting period. Mice were killed after each exposure week. Skin biopsies and blood were obtained for histological study, RNA isolation and antibody analysis.
  
  
  RESULTS
  There was a progressive and significant thickening of the epidermis and dermis in OVA-exposed mice. Significantly increased dermal cell infiltration of eosinophils, mast cells and total inflammatory cells, including CD3 and CD4 cells, was found after each OVA exposure week. Total IgE, IgG2a and OVA-specific IgE were significantly increased after the second and third exposure week, while OVA-specific IgG2a was significantly induced after the third exposure week. Gradual and/or significant increases in mRNA expression of IL-1beta, TNF-alpha, IL-4, IL-10, IL-13, IFN-gamma and IL-12p35 were found after each exposure week. Chemokines and their receptors involved in both T-helper type 1 (Th1)- and Th2-type cell recruitment (CCL1, CCL8, CCL11, CCL24, CXCL9, CXCL10, CCR1, CCR3, CCR5, CCR8 and CXCR3) were up-regulated significantly at different time-points.
  
  
  CONCLUSIONS
  This study provides an insight into the dynamic nature and time-dependent transition of skin inflammation and systemic immune responses in a murine AD model induced by repeated epicutaneous exposures to OVA.
authors.affiliation: Unit of Excellence in Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Savinko
authors.forename: H
authors.initials: H
authors.lastname: Wolff
authors.forename: M C
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: L
authors.initials: L
authors.lastname: Kemeny
authors.forename: B
authors.initials: B
authors.lastname: Homey
authors.forename: A I
authors.initials: AI
authors.lastname: Lauerma
authors.forename: H
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin / Q000009:adverse effects*; D012867:Skin / Q000276:immunology* / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D000485:Allergens; D010047:Ovalbumin