title: Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes.
abstract: BACKGROUND
  The identification of filaggrin mutations has contributed towards our understanding of hereditary factors associated with epidermal dysfunction observed in individuals with atopic eczema (AE). However, factors that predispose to acquired filaggrin modulation are not well understood. Interleukin (IL)-22 is upregulated in lesional AE tissue, but its effects on filaggrin expression and genes associated with epidermal function have not yet been comprehensively addressed.
  
  
  OBJECTIVE
  To investigate the effects of IL-22 on expression of filaggrin and genes encoding proteins relevant to epidermal function.
  
  
  METHODS
  Microarray analysis was performed on IL-22-stimulated HaCaT keratinocytes. Filaggrin protein level was assessed by an intracellular enzyme-linked immunosorbent assay (ELISA) and Western blot in HaCaT cells and the findings were validated in primary keratinocytes.
  
  
  RESULTS
  Exposure to IL-22 cytokine resulted in a downregulation of profilaggrin mRNA expression in HaCaT keratinocytes. The expression of genes involved in enzymatic processing of profilaggrin as well as the generation of natural moisturizing factor was also altered. Furthermore, there was an upregulation of many transcripts encoding proteins of the S100 family. Profilaggrin/filaggrin downregulation was detected by intracellular ELISA and Western blot in HaCaT cells. The relevance to the primary setting was confirmed in primary keratinocytes by Western blot.
  
  
  CONCLUSIONS
  IL-22 downregulates profilaggrin/filaggrin expression in keratinocytes at both mRNA and protein levels and affects genes relevant to epidermal function. This novel pathway may have relevance to the pathogenesis and treatment of atopic and other skin disease.
authors.affiliation: MRC Human Immunology Unit, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gutowska-Owsiak
authors.forename: A L
authors.initials: AL
authors.lastname: Schaupp
authors.forename: M
authors.initials: M
authors.lastname: Salimi
authors.forename: S
authors.initials: S
authors.lastname: Taylor
authors.forename: G S
authors.initials: GS
authors.lastname: Ogg
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D000091344:Filaggrin Proteins; D015870:Gene Expression; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D004798:Enzymes; D000091344:Filaggrin Proteins; D007378:Interleukins; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D000097043:Interleukin-22; C000717249:FLG protein, human