title: IL-17C and its receptor IL-17RA/IL-17RE identify human oral epithelial cell as an inflammatory cell in recurrent aphthous ulcer.
abstract: BACKGROUND
  Recurrent aphthous ulcer (RAU) is an ulcerative disease of non-keratinized oral mucosa. Colon and bronchial epithelial cells produce interleukin-17C (IL-17C) upon stimulation of Toll-like receptor 2 (TLR2), TLR3 and TLR5, which are highly expressed in epithelial cells in RAU lesions. We therefore investigated the eventual presence and function of IL-17C in cultured human oral keratinocytes (HOK) and control biopsies compared to RAU lesions.
  
  
  METHODS
  Expression of IL-17A, IL-17C, IL-17RA and IL-17RE was analysed in cultured HOK cells using quantitative real-time polymerase chain reaction (qRT-PCR). HOK cells were stimulated with IL-17C and analysed for IL-8 and tumour necrosis factor-α (TNF-α) using qRT-PCR. Control mucosa (n = 5) was immunostained for IL-17A, IL-17C, IL-8, TNF-α and mast cell tryptase and compared with RAU lesions (n = 5) using the mean grey scale value.
  
  
  RESULTS
  IL-17C, but no IL-17A, mRNA was found in cultured HOK cells. Components of the heterodimeric IL-17RA/IL-17RE receptor for IL-17C were also highly expressed. Stimulation of HOK with IL-17C increased TNF-α mRNA (P = 0.03; IL-8 increase was not statistically significant). HOK in RAU lesions stained intensively for IL-17C compared to controls (P = 0.006). This was associated with increased epithelial immunostaining of TNF-α (P = 0.04) and IL-8 (P = 0.02). Most of the inflammatory cells which stained for IL-17A in control mucosa and RAU lesions were also mast cell tryptase positive.
  
  
  CONCLUSIONS
  IL-17C is highly expressed in epithelial cells in RAU lesions, where it seems to stimulate oral keratinocytes via IL-17RA/IL-17RE to produce pro-inflammatory cytokines. Human oral epithelial cells are probably important inflammatory cells in RAU.
authors.affiliation: Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland; Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Samadi
authors.forename: Vesa-Petteri
authors.initials: VP
authors.lastname: Kouri
authors.forename: Abdelhakim
authors.initials: A
authors.lastname: Salem
authors.forename: Mari
authors.initials: M
authors.lastname: Ainola
authors.forename: Emilia
authors.initials: E
authors.lastname: Kaivosoja
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Barreto
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Hietanen
authors.forename: Ritva
authors.initials: R
authors.lastname: Häyrinen-Immonen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002648:Child; D004847:Epithelial Cells / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis* / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis; D015603:Keratinocytes / Q000276:immunology*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D053722:Receptors, Interleukin-17 / Q000032:analysis*; D013281:Stomatitis, Aphthous / Q000276:immunology / Q000473:pathology*; D053802:Tryptases / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; C508717:IL17A protein, human; C515925:IL17C protein, human; C109985:IL17RA protein, human; C548677:IL17REL protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D053722:Receptors, Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D053802:Tryptases
keywords: innate immunity; interleukin-17A; interleukin-17C; oral epithelial cells; recurrent aphthous ulcer