Oral rehabilitation aims to restore the aesthetic and function of the stomatognathic and phonetic systems, providing quality of life for the patients. To reach this objective, dental implants have been applied with high rates of success (Moraschini, Velloso, Luz, & Porto-Barboza, 2015; Nicoli et al., 2017). Nevertheless, placing implants in the correct position by freehand conventional techniques is chal

Short-chain fatty acids (SCFA) are bacterial metabolites that can be found in periodontal pockets. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) within the epithelium pocket is considered to be a key event for the selective transmigration of leucocytes towards the gingival sulcus. However, the impact of SCFA on ICAM-1 expression by oral epithelial cells remains unclear. We therefore exposed the oral squamous carcinoma cell line HSC-2, primary oral epithelial cells and human gingival fibroblasts to SCFA, namely acetate, propionate and butyrate, and stimulated with known inducers of ICAM-1 such as interleukin-1-beta (IL1β) and tumor necrosis factor-alfa (TNFα). We report here that butyrate but not acetate or propionate significantly suppressed the cytokine-induced ICAM-1 expression in HSC-2 epithelial cells and primary epithelial cells. The G-protein coupled receptor-43 (GPR43/ FFAR2) agonist but not the histone deacetylase inhibitor, trichostatin A, mimicked the butyrate effects. Butyrate also attenuated the nuclear translocation of p65 into the nucleus on HSC-2 cells. The decrease of ICAM-1 was independent of Nrf2/HO-1 signaling and phosphorylation of JNK and p38. Nevertheless, butyrate could not reverse an ongoing cytokine-induced ICAM-1 expression in HSC-2 cells. Overall, these observations suggest that butyrate can attenuate cytokine-induced ICAM-1 expression in cells with epithelial origin.Int. J. Mol. Sci. 2020, 21, 1679 2 of 15 crevicular fluid by means of a tightly controlled expression of adhesion molecules, thereby defending microbiological antagonism in the periodontal tissue [2,3]. Thus, the increase of adhesion molecules by inflammatory mediators has to be counterbalanced by local cues to control an excessive influx of cells of the innate immune system.The influx of cells is controlled by intercellular adhesion molecule-1 (ICAM-1), allowing the transmigration of leucocytes which express the corresponding lymphocyte function-associated antigen-1 and macrophage adhesion ligand-1 [4]. ICAM-1, being induced by inflammatory cues such as interleukin-1-beta (IL1β) and tumor necrosis factor-α (TNFα) [5], is expressed by the vascular endothelium and by the junctional epithelium [6], thus, facilitating transmigration of leukocytes across vascular endothelia and the invasion of the extracellular matrix [7]. Although ICAM-1 is consistently expressed by junctional epithelial cells in healthy gingiva and in pocket epithelium, it is not detectable on the majority of keratinocytes in the external gingival epithelium [6,8]. The question then arises, how is the expression of ICAM-1 in epithelial cells controlled?The increase of ICAM-1 expression by inflammatory cues is evidently well-documented. Inflammatory mediators including IL-6 and prostaglandin E 2 increase ICAM-1 expression in human oral squamous cell carcinoma SCC4 cells in vitro [9,10]. Primary gingival epithelial cells increasingly express ICAM-1 upon inflammatory cytokines stimuli, namely, TNFα and interferon-γ [11]....

Short-chain fatty acids (SCFA), bacterial metabolites released from dental biofilm, are supposed to target the oral epithelium. There is, however, no consensus on how SCFA affect the oral epithelial cells. The objective of the present study was to systematically review the available in vitro evidence of the impact of SCFA on human oral epithelial cells in the context of periodontal disease. A comprehensive electronic search using five databases along with a grey literature search was performed. In vitro studies that evaluated the effects of SCFA on human oral epithelial cells were eligible for inclusion. Risk of bias was assessed by the University of Bristol’s tool for assessing risk of bias in cell culture studies. Certainty in cumulative evidence was evaluated using GRADE criteria (grading of recommendations assessment, development, and evaluation). Of 3591 records identified, 10 were eligible for inclusion. A meta-analysis was not possible due to the heterogeneity between the studies. The risk of bias across the studies was considered “serious” due to the presence of methodological biases. Despite these limitations, this review showed that SCFA negatively affect the viability of oral epithelial cells by activating a series of cellular events that includes apoptosis, autophagy, and pyroptosis. SCFA impair the integrity and presumably the transmigration of leucocytes through the epithelial layer by changing junctional and adhesion protein expression, respectively. SCFA also affect the expression of chemokines and cytokines in oral epithelial cells. Future research needs to identify the underlying signaling cascades and to translate the in vitro findings into preclinical models.