Al-Samadi Ahmed, Kouri Vesa-Petteri, Salem Abdelhakim, Ainola Mari, Kaivosoja Emilia, Barreto Gonçalo, Konttinen Yrjö T, Hietanen Jarkko, Häyrinen-Immonen Ritva
Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland; Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
J Oral Pathol Med. 2014 Feb;43(2):117-24. doi: 10.1111/jop.12095. Epub 2013 Jul 3.
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.
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.
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.
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.
复发性阿弗他溃疡（RAU）是一种发生于非角化口腔黏膜的溃疡性疾病。结肠和支气管上皮细胞在Toll样受体2（TLR2）、TLR3和TLR5受到刺激后会产生白细胞介素-17C（IL-17C），而这些受体在RAU病变的上皮细胞中高度表达。因此，我们研究了与RAU病变相比，培养的人口腔角质形成细胞（HOK）及对照活检组织中IL-17C的最终存在情况及其功能。
采用定量实时聚合酶链反应（qRT-PCR）分析培养的HOK细胞中IL-17A、IL-17C、IL-17RA和IL-17RE的表达。用IL-17C刺激HOK细胞，并使用qRT-PCR分析其IL-8和肿瘤坏死因子-α（TNF-α）水平。对对照黏膜（n = 5）进行IL-17A、IL-17C、IL-8、TNF-α和肥大细胞类胰蛋白酶的免疫染色，并使用平均灰度值与RAU病变（n = 5）进行比较。
在培养的HOK细胞中发现了IL-17C的mRNA，但未发现IL-17A的mRNA。IL-17C异二聚体受体IL-17RA/IL-17RE的组成成分也高度表达。用IL-17C刺激HOK细胞可使TNF-α mRNA增加（P = 0.03；IL-8增加无统计学意义）。与对照组相比，RAU病变中的HOK细胞对IL-17C染色强烈（P = 0.006）。这与TNF-α（P = 0.04）和IL-8（P = 0.02）的上皮免疫染色增加有关。在对照黏膜和RAU病变中，大多数对IL-17A染色的炎性细胞也是肥大细胞类胰蛋白酶阳性。
IL-17C在RAU病变的上皮细胞中高度表达，似乎通过IL-17RA/IL-17RE刺激口腔角质形成细胞产生促炎细胞因子。人口腔上皮细胞可能是RAU中重要的炎性细胞。
