Reduced filaggrin expression is accompanied by increased Staphylococcus aureus colonization of epidermal skin models

Clin Exp Allergy. 2014 Dec;44(12):1515-24. doi: 10.1111/cea.12443.

Abstract

Background: Atopic dermatitis is an inflammatory skin disease that is characterized by a reduced skin barrier function, reduced filaggrin (FLG) expression as well as increased colonization by Staphylococcus aureus.

Objective: This study focused on the possible involvement of FLG in epidermal colonization by S. aureus and/or whether it affects the epidermal defence mechanisms, including the expression of antimicrobial peptides (AMPs) and enzymes involved in stratum corneum barrier lipid synthesis. Furthermore, IL-31 has been shown to reduce FLG expression, but its effects on bacterial colonization and on the expression of AMPs and enzymes involved in the barrier lipid synthesis are not known.

Material and methods: We established N/TERT-based epidermal models (NEMs), after FLG knockdown (FLG-KD) and/or cultured with IL-31, that were colonized with S. aureus for 24 h.

Results: Both FLG-KD and IL-31 supplementation resulted in significantly increased epidermal S. aureus colonization, as well as in an up-regulation of S. aureus-induced IL-8 expression. IL-31, but not FLG-KD, prevented S. aureus-induced up-regulation of mRNA expression for the AMPs human β-defensin 2 and -3 and RNAse7, whereas psoriasin expression remained unchanged. Furthermore, the S. aureus colonization induced changes in mRNA expression of ELOVL4 was not affected by FLG-KD, but was blocked by IL-31. Expression of SCD-1 and Gcase mRNA was reduced by IL-31, but not by FLG-KD.

Conclusion: This study shows that NEMs, with FLG-KD and/or cultured in the presence of IL-31, mimic the skin of patients with atopic dermatitis in several aspects, including enhanced bacterial colonization, increased inflammatory and reduced protective responses.

Keywords: IL-31; Staphylococcus aureus; epidermal model; filaggrin; skin barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Animals
  • Cell Line
  • Dermatitis, Atopic / etiology
  • Disease Models, Animal
  • Epidermis / metabolism*
  • Epidermis / microbiology*
  • Epidermis / pathology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Interleukin-8 / metabolism
  • Interleukins / pharmacology
  • Intermediate Filament Proteins / genetics*
  • Lipids / biosynthesis
  • Staphylococcal Infections / complications*
  • Staphylococcal Infections / genetics*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus*

Substances

  • IL31 protein, human
  • Interleukin-8
  • Interleukins
  • Intermediate Filament Proteins
  • Lipids
  • filaggrin
  • Adenosine Monophosphate