IL-1β strengthens the physical barrier in gingival epithelial cells

Abstract

Periodontitis is one of the most common oral diseases worldwide and is caused by a variety of interactions between oral bacteria and the host. Here, pathogens induce inflammatory host responses that cause the secretion of proinflammatory cytokines such as IL-1β, IL-6, and IL-8 by oral epithelial cells. In various systems, it has been shown that inflammation compromises physical barriers, which enables bacteria to invade the tissue. In this study, we investigated the barrier properties of the oral mucosa under physiological and inflamed conditions. For this purpose, we assessed the influence of IL-1β on the transepithelial electrical resistance and in particular on tight junctions in vitro in human stratified squamous epithelium models. Indirect immunofluorescence and western blot analyses were performed to investigate localization and expression of tight junction proteins in primary gingival cells, immortalized gingival cells and native gingiva. Furthermore, the TEER of gingival keratinocytes was assessed. The results showed that IL-1β led to strengthening of the gingival keratinocyte barrier. This was demonstrated by an increase in TEER, the upregulation of TJ proteins, and an increase in the formation of TJ strands. The IL-1β-mediated upregulation of occludin was prevented by the NF-κB inhibitor BAY 11-7085. These observations provide insights into host responses in the early stages of periodontal disease and offer information about TJ formation in human gingival epithelial cells under physiological and inflammatory conditions. Comprehensive knowledge of the physical barrier during inflammation may help in developing strategies to effectively target the inflammatory barrier to improve the bioavailability of drugs for the treatment of periodontitis.

Upregulation of psoriasin/S100A7 correlates with clinical severity in patients with oral lichen planus

“…The oral mucosa provides a primary physical barrier, which is achieved by a high degree of differentiation and cell-cell linkages of the epithelial cells, known as tight junctions (TJ). Studies on oral epithelia have shown that pro-inflammatory cytokines can alter the physical barrier, such as specific expression of TJ proteins [ 27 ]. Moreover, alterations of the epithelial barrier with disturbances in desmosomes, adherens and tight junctions in OLP have been reported [ 28 ].…”

Anti-inflammatory IL-8 Regulation via an Advanced Drug Delivery System at the Oral Mucosa

“…For cell culture experiments, hTERT-immortalized human gingival keratinocytes (OKG4/bmi1/TERT) kindly provided by Susan Gibbs were used. − Primary gingival epithelial cells (GECs) and fibroblasts (GF) were dissected from oral mucosal tissues, obtained from oral and periodontal surgery in the Department of Periodontology, Oral Medicine, and Oral Surgery (Charité – Universitätsmedizin Berlin), and it was approved by the institutional review board (EA/185/16). Epithelial cells were cultured and differentiated with the same media and reagents as described by our group . For the 3D mucosa organoids, fibroblasts (immortalized, IhGF; primary human, GF) were co-cultured with OKG4 or primary GECs, respectively.…”

“…Gene expression of the cytokines TNFα, IL-1β, IL-6, and IL-8 was determined and normalized to the housekeeping gene GAPDH. Relative gene expression was determined via the delta–delta Ct method . The primers were purchased from Metabion GmbH (Planegg/Steinkirchen, Germany).…”

The Role of the Innate Immune Response in Oral Mucositis Pathogenesis

“…Salivary gland function and saliva composition is rapidly altered in response to cancer therapies and impairs the ability to retain optimal conditions to balance microbial and epithelial interactions, including compositional shifts in the oral microbiome [31]. Epithelial cells lining the oral cavity express a range of innate immune sensors that mediate signals between microbes and immune cells [32] and have been shown to be major contributors of IL-1β secretion during oral inflammation [33]. IL-1β has attracted major attention in OM research due to its diverse role in injury development and inflammatory signals [34,35].…”