title: Role of fibroblasts in the pathogenesis of atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a common dermatosis that highly impairs a patient's quality of life. The recent discovery that epidermal barrier defects caused by an aberrant differentiation process of keratinocytes are comparably important to the well-characterized changes in immune response patterns attributed a crucial role to the keratinocytes. Fibroblasts are able to alter proliferation and differentiation of keratinocytes, but their role in AD is not yet fully understood.
  
  
  OBJECTIVE
  We sought to determine the role of fibroblasts in skin proliferation and differentiation in patients with AD.
  
  
  METHODS
  We used human 3-dimensional organotypic skin cultures consisting of atopic fibroblasts and healthy keratinocytes, as well as healthy fibroblasts and atopic keratinocytes, and compared them with their controls. The expression of differentiation markers in these organotypic cultures were analyzed by using immunohistology and quantitative RT-PCR. Furthermore, the fundamental role of fibroblast-secreted leukemia inhibitory factor was assessed by using small interfering RNA-mediated knockdown cultures.
  
  
  RESULTS
  We observed that atopic fibroblasts influence the proliferation of keratinocytes and the terminal differentiation process, resulting in an in vivo-like morphology of AD. Subsequently, healthy fibroblasts were able to restore the structural deficits of the epidermis consisting of atopic keratinocytes. Partially, these effects were due to a reduced expression of the differentiation-associated cytokine leukemia inhibitory factor by atopic fibroblasts.
  
  
  CONCLUSIONS
  These data demonstrate that fibroblasts and the modulation of fibroblast-derived factors might be new therapeutic targets for the alleviation of AD.
authors.affiliation: Research and Development, Beiersdorf AG, Hamburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Berroth
authors.forename: Jochen
authors.initials: J
authors.lastname: Kühnl
authors.forename: Nina
authors.initials: N
authors.lastname: Kurschat
authors.forename: Agatha
authors.initials: A
authors.lastname: Schwarz
authors.forename: Franz
authors.initials: F
authors.lastname: Stäb
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Gitta
authors.initials: G
authors.lastname: Neufang
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D049109:Cell Proliferation; D003876:Dermatitis, Atopic / Q000209:etiology*; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D046509:Tissue Culture Techniques
chemical_list: D053605:Leukemia Inhibitory Factor