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.
Conclusion
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.