Detectable Dioxins in Human Saliva and Their Effects on Gingival Epithelial Cells

Dioxin, a powerful hormone-disrupting chemical, exhibits serious health effects when it reaches body fat. Here we analyzed coplanar polychlorinated biphenyls (PCBs) and polychlorinated-dibenzo- p-dioxins (PCDDs) in human saliva as compared with blood specimens, and examined their effects on human gingival epithelial cells (HGEC). High levels of tri- and tetrachlorinated PCBs were found in saliva, whereas we detected predominantly hexa- and heptachlorinated PCBs in blood. Among PCDDs, the saliva and blood specimens contained mainly 1,2,3,4,6,7,8,9-octachlorodibenzo- p-dioxin (OCDD). Among the toxic dioxins proposed by the World Health Organization (WHO) in 1998, 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118) and OCDD, which were mainly found in saliva, significantly induced IL-8 production in HGEC. Furthermore, these two dioxins markedly augmented IL-8 production stimulated with fimbriae from Porphyromonas gingivalis, which is well-known as a pathogenic factor in periodontal diseases. These results suggest that dioxins in saliva may be a risk factor for periodontal diseases.

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Possible Roles of IL-33 in Periodontal Diseases: Porphyromonas gingivalis Induced IL-33 in Human Gingival Epithelial Cells

Interface Oral Health Science 2014 ◽

10.1007/978-4-431-55192-8_25 ◽

2015 ◽

pp. 293-303

Author(s):

Hiroyuki Tada ◽

Hidetoshi Shimauchi ◽

Haruhiko Takada ◽

Kenji Matsushita

Keyword(s):

Epithelial Cells ◽

Porphyromonas Gingivalis ◽

Periodontal Diseases ◽

Gingival Epithelial Cells ◽

Human Gingival Epithelial Cells

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Oral Treponemes and Their Outer Membrane Extracts Activate Human Gingival Epithelial Cells through Toll-Like Receptor 2

Infection and Immunity ◽

10.1128/iai.71.2.717-725.2003 ◽

2003 ◽

Vol 71 (2) ◽

pp. 717-725 ◽

Cited By ~ 40

Author(s):

Yasuyuki Asai ◽

Takayoshi Jinno ◽

Tomohiko Ogawa

Keyword(s):

Monoclonal Antibody ◽

Epithelial Cells ◽

Mrna Expression ◽

Outer Membrane ◽

Periodontal Diseases ◽

Treponema Denticola ◽

Toll Like Receptor ◽

Gingival Epithelial Cells ◽

Toll Like Receptor 2 ◽

Human Gingival Epithelial Cells

ABSTRACT Oral treponemes are considered to be important in the development and progression of periodontal diseases. We investigated the mechanisms of recognition and activation of human gingival epithelial cells (HGEC) with the oral treponemes Treponema denticola, Treponema vincentii, and Treponema medium and their outer membrane extracts (OMEs). T. vincentii and T. medium but not T. denticola produced interleukin 8 (IL-8) in an HGEC culture. Further, all three treponemes induced IL-8 mRNA expression and NF-κB activation in HGEC. Among them, T. denticola especially exhibited trypsin- and chymotrypsin-like protease activities, and the addition of chymostatin, a chymotrypsin protease inhibitor, resulted in detectable IL-8 production by HGEC cultured with T. denticola. Additionally, IL-8 mRNA expression in HGEC cultured with the three treponemes and their OMEs was definitely inhibited by the mouse anti-human Toll-like receptor 2 (TLR2) monoclonal antibody TL2.1. These findings suggest that oral treponemes and their OMEs activate HGEC through TLR2.

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Bacterial Fimbriae and Their Peptides Activate Human Gingival Epithelial Cells through Toll-Like Receptor 2

Infection and Immunity ◽

10.1128/iai.69.12.7387-7395.2001 ◽

2001 ◽

Vol 69 (12) ◽

pp. 7387-7395 ◽

Cited By ~ 140

Author(s):

Yasuyuki Asai ◽

Yoshinori Ohyama ◽

Keika Gen ◽

Tomohiko Ogawa

Keyword(s):

Epithelial Cells ◽

Lipid A ◽

Periodontal Diseases ◽

Host Responses ◽

Central Component ◽

Toll Like Receptor ◽

Common Component ◽

Fimbrial Subunit ◽

Gingival Epithelial Cells ◽

Human Gingival Epithelial Cells

ABSTRACT Gingival epithelial cells are a central component of the barrier between oral microflora and internal tissues. Host responses to periodontopathic bacteria and surface components containing fimbriae are thought to be important in the development and progression of periodontal diseases. To elucidate this mechanism, we established immortalized human gingival epithelial cells (HGEC) that were transfected with human papillomavirus. HGEC predominantly expressed Toll-like receptor (TLR) 2, but not TLR4 or CD14. They also induced interleukin-8 (IL-8) production when stimulated withPorphyromonas gingivalis fimbriae andStaphylococcus aureus peptidoglycan, but notEscherichia coli-type synthetic lipid A. Furthermore, an active synthetic peptide composed of residues 69 to 73 (ALTTE) of the fimbrial subunit protein, derived from P. gingivalis and similar to a common component of cell wall peptidoglycans in parasitic bacteria,N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP), significantly induced IL-8 production and NF-κB activation in HGEC, and these cytokine-producing activities were augmented by a complex of soluble CD14 and lipopolysaccharide-binding protein (LBP). IL-8 production in HGEC stimulated with these bacterial components was clearly inhibited by mouse monoclonal antibody to human TLR2. These findings suggest that P. gingivalis fimbrial protein and its active peptide are capable of activating HGEC through TLR2.

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Possible requirement of intercellular adhesion molecule-1 for invasion of gingival epithelial cells byTreponema medium

Canadian Journal of Microbiology ◽

10.1139/w07-094 ◽

2007 ◽

Vol 53 (11) ◽

pp. 1232-1238 ◽

Cited By ~ 3

Author(s):

Riyoko Tamai ◽

Yasuyuki Asai ◽

Atsushi Kawabata ◽

Toshitaka Akisaka ◽

Tomohiko Ogawa

Keyword(s):

Epithelial Cells ◽

Adhesion Molecule ◽

Periodontal Diseases ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Principal Role ◽

Gingival Epithelial Cells ◽

Toll Like Receptor 2 ◽

Human Gingival Epithelial Cells

Oral treponemes are members of the spirochete family of bacteria associated with periodontal diseases. In the present study, we demonstrate that intercellular adhesion molecule-1 (ICAM-1) on human gingival epithelial cells (HGEC) contributed to the invasion of Treponema medium , a medium-sized oral Treponema, into those cells. The quantity of T. medium in HGEC was found to peak at 2 h after inoculation and then decreased gradually. Immunofluorescence microscopy findings showed that the bacteria were colocalized with ICAM-1 on HGEC. Furthermore, knockdown of ICAM-1 in HGEC resulted in inhibition of T. medium invasion by RNA interference, whereas that of Toll-like receptor 2 did not. These results suggest that ICAM-1 may be required for the invasion of T. medium into HGEC, and they indicate that the molecule plays a principal role in the primary stages of the development and progression of chronic periodontitis.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22147669 ◽

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.

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Characterizing the Qatar advanced-phase SARS-CoV-2 epidemic

Scientific Reports ◽

10.1038/s41598-021-85428-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Laith J. Abu-Raddad ◽

Hiam Chemaitelly ◽

Houssein H. Ayoub ◽

Zaina Al Kanaani ◽

Abdullatif Al Khal ◽

...

Keyword(s):

Ad Hoc ◽

Case Fatality ◽

Epidemiologic Studies ◽

World Health ◽

Residential Areas ◽

Antibody Prevalence ◽

Advanced Phase ◽

Cumulative Rate ◽

Blood Specimens ◽

Health Organization

AbstractThe overarching objective of this study was to provide the descriptive epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Qatar by addressing specific research questions through a series of national epidemiologic studies. Sources of data were the centralized and standardized national databases for SARS-CoV-2 infection. By July 10, 2020, 397,577 individuals had been tested for SARS-CoV-2 using polymerase-chain-reaction (PCR), of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI 27.8–28.1%). As of July 5, case severity rate, based on World Health Organization (WHO) severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Age was by far the strongest predictor of severe, critical, or fatal infection. PCR positivity of nasopharyngeal/oropharyngeal swabs in a national community survey (May 6–7) including 1,307 participants was 14.9% (95% CI 11.5–19.0%); 58.5% of those testing positive were asymptomatic. Across 448 ad-hoc testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI 13.7–17.7%). SARS-CoV-2 antibody prevalence was 24.0% (95% CI 23.3–24.6%) in 32,970 residual clinical blood specimens. Antibody prevalence was only 47.3% (95% CI 46.2–48.5%) in those who had at least one PCR positive result, but 91.3% (95% CI 89.5–92.9%) among those who were PCR positive > 3 weeks before serology testing. Qatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to growing immunity levels in the population.

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Pro-inflammatory cytokine responses in human gingival epithelial cells after stimulation with cell wall extract of Aggregatibacter actinomycetemcomitans subtypes

Anaerobe ◽

10.1016/j.anaerobe.2017.08.001 ◽

2017 ◽

Vol 48 ◽

pp. 103-109 ◽

Cited By ~ 5

Author(s):

Nuntiya Pahumunto ◽

Pareena Chotjumlong ◽

Anupong Makeudom ◽

Suttichai Krisanaprakornkit ◽

Gunnar Dahlen ◽

...

Keyword(s):

Cell Wall ◽

Epithelial Cells ◽

Inflammatory Cytokine ◽

Aggregatibacter Actinomycetemcomitans ◽

Cytokine Responses ◽

Gingival Epithelial Cells ◽

Cell Wall Extract ◽

Human Gingival Epithelial Cells

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

Infection and Immunity ◽

10.1128/iai.72.7.3752-3758.2004 ◽

2004 ◽

Vol 72 (7) ◽

pp. 3752-3758 ◽

Cited By ~ 34

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.

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