scholarly journals Aggregatibacter actinomycetemcomitans Biofilm Reduces Gingival Epithelial Cell Keratin Expression in an Organotypic Gingival Tissue Culture Model

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 278 ◽  
Author(s):  
Arzu Beklen ◽  
Annamari Torittu ◽  
Riikka Ihalin ◽  
Marja Pöllänen
Keyword(s):  
Epithelial Cells ◽  
Structural Integrity ◽  
Close Contact ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Gingival Tissue ◽  
Gingival Epithelial Cell ◽  
Keratin Expression ◽  
Gingival Epithelial Cells ◽  
Dividing Cells ◽  
Gingival Mucosa

Epithelial cells express keratins, which are essential for the structural integrity and mechanical strength of the cells. In the junctional epithelium (JE) of the tooth, keratins such as K16, K18, and K19, are expressed, which is typical for non-differentiated and rapidly dividing cells. The expression of K17, K4, and K13 keratins can be induced by injury, bacterial irritation, smoking, and inflammation. In addition, these keratins can be found in the sulcular epithelium and in the JE. Our aim was to estimate the changes in K4, K13, K17, and K19 expression in gingival epithelial cells exposed to Aggregatibacter actinomycetemcomitans. An organotypic gingival mucosa and biofilm co-culture was used as a model system. The effect of the biofilm after 24 h was assessed using immunohistochemistry. The structure of the epithelium was also studied with transmission electron microscopy (TEM). The expression of K17 and K19, as well as total keratin expression, decreased in the suprabasal layers of epithelium, which were in close contact with the A. actinomycetemcomitans biofilm. The effect on keratin expression was biofilm specific. The expression of K4 and K13 was low in all of the tested conditions. When stimulated with the A. actinomycetemcomitans biofilm, the epithelial contact site displayed a thick necrotic layer on the top of the epithelium. The A. actinomycetemcomitans biofilm released vesicles, which were found in close contact with the epithelium. After A. actinomycetemcomitans irritation, gingival epithelial cells may lose their resistance and become more vulnerable to bacterial infection.

Key Elements of Gingival Epithelial Homeostasis upon Bacterial Interaction

2020 ◽  
pp. 002203452097301
Author(s):  
J.S. Lee ◽  
Ö. Yilmaz
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Functional Roles ◽  
Gingival Epithelial Cell ◽  
Opportunistic Bacteria ◽  
Gingival Epithelial Cells ◽  
Diseased State ◽  
Gingival Mucosa ◽  
External Stimuli

Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as Porphyromonas gingivalis, through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostatic metabolic pathways for successful bacterial persistence. As the overgrowth of colonizing microorganisms in the gingival mucosa can shift from homeostasis to dysbiosis or a diseased state, it is crucial to understand how the innate modulatory molecules are intricately involved in antibacterial pathways and how they shape susceptibility versus resistance in the epithelium toward pathogens. Thus, in this review, we highlight recent discoveries in gingival epithelial cell research in the context of bacterial colonizers. The current knowledge outlined here demonstrates the ability of epithelial cells to possess highly organized defense machineries, which can jointly regulate host-derived danger molecule signaling and integrate specific global responses against opportunistic bacteria to combat microbial incursion and maintain host homeostatic balance. These novel examples collectively suggest that the oral epithelia are equipped with a dynamically robust and interconnected defense system encompassing sensors and various effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria.

scholarly journals Mobilization of TLR4 Into Lipid Rafts by Aggregatibacter Actinomycetemcomitans in Gingival Epithelial Cells

2016 ◽  
Vol 39 (5) ◽  
pp. 1777-1786 ◽  
Author(s):  
Haruka Imai ◽  
Tsuyoshi Fujita ◽  
Mikihito Kajiya ◽  
Kazuhisa Ouhara ◽  
Tetsuya Yoshimoto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Map Kinase ◽  
Lipid Rafts ◽  
Inflammatory Cytokines ◽  
Aggregatibacter Actinomycetemcomitans ◽  
P38 Map Kinase ◽  
Mrna Levels ◽  
Periodontal Pathogens ◽  
Gingival Epithelial Cells ◽  
Tnf Α

Background: An investigation of the mechanisms underlying the production of inflammatory cytokines through the stimulation of microorganisms on gingival epithelial cells may provide insights into the pathogenesis of the initiation of periodontitis. Lipid rafts, microdomains in the cell membrane, include a large number of receptors, and are centrally involved in signal transduction. We herein examined the involvement of lipid rafts in the expression of interleukin (IL-6) and IL-8 in gingival epithelial cells stimulated by periodontal pathogens. Methods: OBA9, a human gingival cell line, was stimulated by Aggregatibacter actinomycetemcomitans or tumor necrosis factor (TNF)-α in the presence of methyl-β-cyclodextrin (MβCD). Results: A. actinomycetemcomitans or TNF-α increased IL-8 and IL-6 mRNA levels, and promoted the phosphorylation of ERK and p38 MAP kinase in OBA9. The pretreatment with MβCD abolished increases in IL-6 and IL-8 mRNA levels and the phosphorylation induced by A. actinomycetemcomitans, but did not suppress the response induced by TNF-α. The transfection of TLR4 inhibited A. actinomycetemcomitans-induced increases in IL-8 and IL-6 mRNA levels. Confocal microscopy revealed that MβCD inhibited the mobilization of TLR4 into lipid rafts. Conclusion: The mobilization of TLR4 into lipid rafts is involved in the expression of inflammatory cytokines and phosphorylation of MAP kinase in human gingival epithelial cells stimulated by A. actinomycetemcomitans.

scholarly journals Smad2 is Involved in Aggregatibacter actinomycetemcomitans-induced Apoptosis

2014 ◽  
Vol 93 (11) ◽  
pp. 1148-1154 ◽  
Author(s):  
T. Yoshimoto ◽  
T. Fujita ◽  
K. Ouhara ◽  
M. Kajiya ◽  
H. Imai ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Type I ◽  
Sirna Transfection ◽  
Periodontopathic Bacteria ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells ◽  
Induced Apoptosis

Apoptosis is thought to contribute to the progression of periodontitis. It has been suggested that the apoptosis of epithelial cells may contribute to the loss of epithelial barrier function. Smad2, a downstream signaling molecule of TGF-β receptors (TGF-βRs), is critically involved in apoptosis in several cell types. However, the relationship between smad2 and bacteria-induced apoptosis has not yet been elucidated. It is possible that the regulation of apoptosis induced by periodontopathic bacteria may lead to novel preventive therapies for periodontitis. Therefore, in the present study, we investigated the involvement of smad2 phosphorylation in apoptosis of human gingival epithelial cells induced by Aggregatibacter actinomycetemcomitans ( Aa). Aa apparently induced the phosphorylation of smad2 in primary human gingival epithelial cells (HGECs) or the human gingival epithelial cell line, OBA9 cells. In addition, Aa induced phosphorylation of the serine residue of the TGF-β type I receptor (TGF-βRI) in OBA9 cells. SB431542 (a TGF-βRI inhibitor) and siRNA transfection for TGF-βRI, which reduced both TGF-βRI mRNA and protein levels, markedly attenuated the Aa-induced phosphorylation of smad2. Furthermore, the disruption of TGF-βRI signaling cascade by SB431542 and siRNA transfection for TGF-βRI abrogated the activation of cleaved caspase-3 expression and repressed apoptosis in OBA9 cells treated with Aa. Thus, Aa induced apoptosis in gingival epithelial cells by activating the TGF-βRI-smad2-caspase-3 signaling pathway. The results of the present study may suggest that the periodontopathic bacteria, Aa, activates the TGF-βR/smad2 signaling pathway in human gingival epithelial cells and induces apoptosis in epithelial cells, which may lead to new therapeutic strategies that modulate the initiation of periodontitis.

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