scholarly journals Distinct Signaling Pathways Between Human Macrophages and Primary Gingival Epithelial Cells by Aggregatibacter actinomycetemcomitans

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 248 ◽  
Author(s):  
Ellen S. Ando-Suguimoto ◽  
Manjunatha R. Benakanakere ◽  
Marcia P.A. Mayer ◽  
Denis F. Kinane
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Responses ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Aggressive Periodontitis ◽  
Host Cells ◽  
Tissue Destruction ◽  
Periodontal Tissues ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells

In aggressive periodontitis, the dysbiotic microbial community in the subgingival crevice, which is abundant in Aggregatibacter actinomycetemcomitans, interacts with extra- and intracellular receptors of host cells, leading to exacerbated inflammation and subsequent tissue destruction. Our goal was to understand the innate immune interactions of A. actinomycetemcomitans with macrophages and human gingival epithelial cells (HGECs) on the signaling cascade involved in inflammasome and inflammatory responses. U937 macrophages and HGECs were co-cultured with A. actinomycetemcomitans strain Y4 and key signaling pathways were analyzed using real-time PCR, Western blotting and cytokine production by ELISA. A. actinomycetemcomitans infection upregulated the transcription of TLR2, TLR4, NOD2 and NLRP3 in U937 macrophages, but not in HGECs. Transcription of IL-1β and IL-18 was upregulated in macrophages and HGECs after 1 h interaction with A. actinomycetemcomitans, but positive regulation persisted only in macrophages, resulting in the presence of IL-1β in macrophage supernatant. Immunoblot data revealed that A. actinomycetemcomitans induced the phosphorylation of AKT and ERK1/2, possibly leading to activation of the NF-κB pathway in macrophages. On the other hand, HGEC signaling induced by A. actinomycetemcomitans was distinct, since AKT and 4EBP1 were phosphorylated after stimulation with A. actinomycetemcomitans, whereas ERK1/2 was not. Furthermore, A. actinomycetemcomitans was able to induce the cleavage of caspase-1 in U937 macrophages in an NRLP3-dependent pathway. Differences in host cell responses, such as those seen between HGECs and macrophages, suggested that survival of A. actinomycetemcomitans in periodontal tissues may be favored by its ability to differentially activate host cells.

scholarly journals Cigarette Smoke Stimulates SARS-CoV-2 Internalization by Activating AhR and Increasing ACE2 Expression in Human Gingival Epithelial Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7669
Author(s):  
Cassio Luiz Coutinho Almeida-da-Silva ◽  
Harmony Matshik Dakafay ◽  
Kaitlyn Liu ◽  
David M. Ojcius
Keyword(s):  
Epithelial Cells ◽  
Oral Cavity ◽  
Cigarette Smoke ◽  
Large Body ◽  
Receptor Expression ◽  
Host Cells ◽  
Dependent Manner ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells ◽  
Oral Cells

A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Here, we examined the effects of cigarette smoke on the expression of SARS-CoV-2 receptors and infection in human gingival epithelial cells (GECs). We found that cigarette smoke condensates (CSC) upregulated ACE2 and TMPRSS2 expression in GECs, and that CSC activated aryl hydrocarbon receptor (AhR) signaling in the oral cells. ACE2 was known to mediate SARS-CoV-2 internalization, and we demonstrate that CSC treatment potentiated the internalization of SARS-CoV-2 pseudovirus in GECs in an AhR-dependent manner. AhR depletion using small interference RNA decreased SARS-CoV-2 pseudovirus internalization in CSC-treated GECs compared with control GECs. Our study reveals that cigarette smoke upregulates SARS-CoV-2 receptor expression and infection in oral cells. Understanding the mechanisms involved in SARS-CoV-2 infection in cells of the oral cavity may suggest therapeutic interventions for preventing viral infection and transmission.

Lipoproteins of Actinomyces viscosus induce inflammatory responses through TLR2 in human gingival epithelial cells and macrophages

2012 ◽  
Vol 14 (11) ◽  
pp. 916-921 ◽  
Author(s):  
Eri Shimada ◽  
Hideo Kataoka ◽  
Yasushi Miyazawa ◽  
Matsuo Yamamoto ◽  
Takeshi Igarashi
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells

scholarly journals Life Below the Gum Line: Pathogenic Mechanisms ofPorphyromonas gingivalis

1998 ◽  
Vol 62 (4) ◽  
pp. 1244-1263 ◽  
Author(s):  
Richard J. Lamont ◽  
Howard F. Jenkinson
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Periodontal Disease ◽  
Regulation Of Gene Expression ◽  
Surface Protein ◽  
Opportunistic Pathogen ◽  
Host Cells ◽  
Transcriptional Level ◽  
Tissue Destruction ◽  
Periodontal Tissues

SUMMARY Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. An opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ecological balance within the complex periodontal microenvironment. Colonization of the subgingival region is facilitated by the ability to adhere to available substrates such as adsorbed salivary molecules, matrix proteins, epithelial cells, and bacteria that are already established as a biofilm on tooth and epithelial surfaces. Binding to all of these substrates may be mediated by various regions of P. gingivalis fimbrillin, the structural subunit of the major fimbriae. P. gingivalis is an asaccharolytic organism, with a requirement for hemin (as a source of iron) and peptides for growth. At least three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive regions of highly conserved sequences, with posttranslational processing of proteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivalis appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells, while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assault on the periodontal tissues, P. gingivalis can modulate eucaryotic cell signal transduction pathways, directing its uptake by gingival epithelial cells. Within this privileged site, P. gingivalis can replicate and impinge upon components of the innate host defense. Although a variety of surface molecules stimulate production of cytokines and other participants in the immune response, P. gingivalis may also undertake a stealth role whereby pivotal immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can be controlled at the transcriptional level. Finally, although periodontal disease is localized to the tissues surrounding the tooth, evidence is accumulating that infection with P. gingivalis may predispose to more serious systemic conditions such as cardiovascular disease and to delivery of preterm infants.

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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