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.

scholarly journals Toll-Like Receptor 2-Mediated Interleukin-8 Expression in Gingival Epithelial Cells by the Tannerella forsythia Leucine-Rich Repeat Protein BspA

2007 ◽  
Vol 76 (1) ◽  
pp. 198-205 ◽  
Author(s):  
Shinsuke Onishi ◽  
Kiyonobu Honma ◽  
Shuang Liang ◽  
Panagiota Stathopoulou ◽  
Denis Kinane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Interleukin 8 ◽  
Host Cells ◽  
Leucine Rich Repeat ◽  
Toll Like Receptor ◽  
Periodontal Pathogens ◽  
Tannerella Forsythia ◽  
Multifunctional Protein ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells

ABSTRACT Tannerella forsythia is a gram-negative anaerobe strongly associated with chronic human periodontitis. This bacterium expresses a cell surface-associated and secreted protein, designated BspA, which has been recognized as an important virulence factor. The BspA protein belongs to the leucine-rich repeat (LRR) and bacterial immunoglobulin-like protein families. BspA is, moreover, a multifunctional protein which interacts with a variety of host cells, including monocytes which appear to respond to BspA through Toll-like receptor (TLR) signaling. Since gingival epithelium forms a barrier against periodontal pathogens, this study was undertaken to determine if gingival epithelial cells respond to BspA challenge and if TLRs play any role in BspA recognition. This study was also directed towards identifying the BspA domains responsible for cellular activation. We provide direct evidence for BspA binding to TLR2 and demonstrate that the release of the chemokine interleukin-8 from human gingival epithelial cells by BspA is TLR2 dependent. Furthermore, the LRR domain of BspA is involved in activation of TLR2, while TLR1 serves as a signaling partner. Thus, our findings suggest that BspA is an important modulator of host innate immune responses through activation of TLR2 in cooperation with TLR1.

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 Identification of Porphyromonas gingivalis Genes Specifically Expressed in Human Gingival Epithelial Cells by Using Differential Display Reverse Transcription-PCR

2004 ◽  
Vol 72 (7) ◽  
pp. 3752-3758 ◽  
Author(s):  
Yoonsuk Park ◽  
Özlem Yilmaz ◽  
Il-Young Jung ◽  
Richard J. Lamont
Keyword(s):  
Epithelial Cells ◽  
Porphyromonas Gingivalis ◽  
Abc Transporter ◽  
Differential Display ◽  
Molecular Mechanisms ◽  
Gene Products ◽  
Reverse Transcription Pcr ◽  
Gingival Epithelial Cells ◽  
Insertional Inactivation ◽  
Human Gingival Epithelial Cells

ABSTRACT Porphyromonas gingivalis, one of the causative agents of adult periodontitis, can invade and survive within host epithelial cells. The molecular mechanisms by which P. gingivalis induces uptake and adapts to an intracellular environment are not fully understood. In this study, we have investigated the genetic responses of P. gingivalis internalized within human gingival epithelial cells (GECs) in order to identify factors involved in invasion and survival. We compared the differential display of arbitrarily PCR-amplified gene transcripts in P. gingivalis recovered from GECs with the display of transcripts in P. gingivalis control cultures. Over 20 potential differentially expressed transcripts were identified. Among these, pepO, encoding an endopeptidase, and genes encoding an ATP-binding cassette (ABC) transporter and a cation-transporting ATPase were upregulated in GECs. To investigate the functionality of these gene products, mutants were generated by insertional inactivation. Compared to the parental strain, mutants of each gene showed a significant reduction in their invasion capabilities. In addition, GEC cytoskeletal responses to the mutants were distinct from those induced by the parent. In contrast, adhesion of the mutant strains to GECs was not affected by lack of expression of the gene products. These results suggest that PepO, a cation-transporting ATPase, and an ABC transporter are required for the intracellular lifestyle of P. gingivalis.

scholarly journals Response of Human Gingival Epithelial Cells (HGE-15) to Bioactive Glass RKKP

2008 ◽  
Vol 7 (1) ◽  
pp. 5-11
Author(s):  
Hitoshi Oguchi ◽  
Yasuyo Karube ◽  
Kameji Matsumoto ◽  
Mitsuhiko Morito
Keyword(s):  
Epithelial Cells ◽  
Bioactive Glass ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells
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