AbstractsMedical & Health Science

The Oral Epithelial Cell: An Active Player in Recurrent Aphthous Ulcers

by Ahmed Al-Samadi




Institution: University of Helsinki
Department: Institute of Clinical Medicine, Faculty of Medicine
Year: 2015
Keywords: dentistry
Record ID: 1140592
Full text PDF: http://hdl.handle.net/10138/154757


Abstract

Recurrent aphthous ulcer (RAU) is an ulcerative disease of the oral mucosa characterised by the appearance of ulcerations in the oral mucosa accompanied by an erythematous halo area surrounding the ulcer and showing signs of acute inflammation. While RAU affects approximately 20% of the population globally, its pathogenesis remains poorly understood. Furthermore, most studies concentrate on treatment while few address the pathogenesis of the disease. This project aimed to determine the mechanisms of oral epithelial cell death in RAU, the role of these cells in disease pathogenesis in terms of toll-like receptor (TLR) expression, and the ability of the these cells to produce chemokines, pro-inflammatory cytokines, and antimicrobial peptides. Together these may first aggravate and, then, down-regulate the inflammation and initiate the healing process. For this purpose, we collected 13 aphthae and 11 healthy control biopsies for immunohistochemical staining, immunofluorescence staining, and quantitative PCR. For functional studies, we cultured primary oral keratinocytes and oral squamous cell carcinoma cell-line SCC-25 and tested their responses to different stimuli. Our results highlight the importance of oral epithelial cells in RAU; interestingly, oral epithelial cells in RAU tested positive for apoptosis markers caspase-3, especially at the superficial and spinous layer, and TUNEL, but negative in controls. We also found that TLRs are primarily present in the basal and suprabasal layers of control epithelium, but their expression extends to the superficial layer in RAU epithelium. Additionally, we found significally higher expressions of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), IL-17C, and beta defensin 2 (BD-2) in RAU oral epithelium compared with control epithelium. Functional studies on cultured primary oral keratinocytes and SCC-25 supported our results from RAU biopsies since these cells responded to damage-associated molecule patterns (DAMPs), such as self-DNA and pro-inflammatory cytokines including IL-17C, TNF-α, and interferon gamma (IFN-γ), through a significant increase in the expression of selected molecules including TLR2, TNF-α, and BD-2. Based on our findings, RAU may begin with a strong initiating factor activating a self-amplificatory cycle. This cycle is characterised by the induction of epithelial cells apoptosis at the superficial layer down to the basal layer, a change in the pattern of TLR distribution, the up-regulation of several chemokines and pro-inflammatory cytokines, and, finally, the secretion of antimicrobial peptides initating the healing process. As a result of the lack of adaptive immunity in RAU, the cycle recurs when the mucosa is subjected to an initiating factor of the same sequence. Toistuva suun alueen haavauma eli afta (RAU) on akuutti tulehdus, joka vaikuttaa suun limakalvolla. Haavauma ilmestyy muutamassa tunnissa ja kestää 5-10 päivää, jonka aikana tulehdus lievittyy ja haava paranee itsestään. Taudille ominaista on limakalvon pintakudoksen…