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

2001 ◽  
Vol 69 (12) ◽  
pp. 7387-7395 ◽  
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.

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

2003 ◽  
Vol 71 (2) ◽  
pp. 717-725 ◽  
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.

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

2003 ◽  
Vol 82 (10) ◽  
pp. 849-853 ◽  
Author(s):  
T. Ogawa ◽  
Y. Asai ◽  
M. Yamashita ◽  
T. Takasuga
Keyword(s):  
Epithelial Cells ◽  
Periodontal Diseases ◽  
Human Saliva ◽  
World Health ◽  
Pathogenic Factor ◽  
Gingival Epithelial Cells ◽  
Coplanar Polychlorinated Biphenyls ◽  
Blood Specimens ◽  
Human Gingival Epithelial Cells ◽  
Health Organization

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.

scholarly journals Metronidazole-Treated Porphyromonas gingivalis Persisters Invade Human Gingival Epithelial Cells and Perturb Innate Responses

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Chuan Wang ◽  
Tianfan Cheng ◽  
Xuan Li ◽  
Lijian Jin
Keyword(s):  
Epithelial Cells ◽  
Porphyromonas Gingivalis ◽  
Present Report ◽  
Well Being ◽  
Host Responses ◽  
Periodontal Health ◽  
Content Type ◽  
Gingival Epithelial Cells ◽  
Human Gingival Epithelial Cells ◽  
Lethal Dosage

ABSTRACT Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like diabetes and cardiovascular disease. Porphyromonas gingivalis as a “keystone” periodontopathogen drives the shift of microbe-host symbiosis to dysbiosis and critically contributes to the pathogenesis of periodontitis. Persisters represent a tiny subset of biofilm-associated microbes highly tolerant to lethal treatment of antimicrobials, and, notably, metronidazole-tolerant P. gingivalis persisters have recently been identified by our group. This study further explored the interactive profiles of metronidazole-treated P. gingivalis persisters (M-PgPs) with human gingival epithelial cells (HGECs). P. gingivalis cells (ATCC 33277) at stationary phase were treated with a lethal dosage of metronidazole (100 μg/ml, 6 h) for generating M-PgPs. The interaction of M-PgPs with HGECs was assessed by microscopy, flow cytometry, cytokine profiling, and quantitative PCR (qPCR). We demonstrated that the overall morphology and ultracellular structure of M-PgPs remained unchanged. Importantly, M-PgPs maintained the capabilities to adhere to and invade HGECs. Moreover, M-PgPs significantly suppressed proinflammatory cytokine expression in HGECs at a level comparable to that seen with the untreated P. gingivalis cells, through the thermosensitive components. The present report reveals that P. gingivalis persisters induced by lethal treatment of antibiotics were able to maintain their capabilities to adhere to and invade human gingival epithelial cells and to perturb the innate host responses. Novel strategies and approaches need to be developed for tackling P. gingivalis and favorably modulating the dysregulated immunoinflammatory responses for oral/periodontal health and general well-being.

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 Treponema denticola Suppresses Expression of Human β-Defensin-3 in Gingival Epithelial Cells through Inhibition of the Toll-Like Receptor 2 Axis

2009 ◽  
Vol 78 (2) ◽  
pp. 672-679 ◽  
Author(s):  
Ji Eun Shin ◽  
Young Sook Kim ◽  
Ju-Eun Oh ◽  
Byung-Moo Min ◽  
Youngnim Choi
Keyword(s):  
Epithelial Cells ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Mitogen Activated Protein Kinase ◽  
Treponema Denticola ◽  
Toll Like Receptor ◽  
Periodontal Pathogens ◽  
Gingival Epithelial Cells ◽  
Toll Like Receptor 2 ◽  
Human Gingival Epithelial Cells

ABSTRACT We reported previously that Treponema denticola, one of the periodontal pathogens, suppresses the expression of human β-defensins (HBDs) in human gingival epithelial cells. To identify the mechanisms involved in this suppression, immortalized and normal human gingival epithelial cells were infected with live or heat-killed T. denticola for 24 h, and then the expression of HBDs was examined by real-time RT-PCR. Live T. denticola suppressed the expression of HBD-3 substantially and also suppressed the expression of HBD-1 and HBD-2. However, heat-killed bacteria did not produce a suppressive effect but instead slightly upregulated the levels of HBD-2 and HBD-3. In contrast to live T. denticola, which reduced the activation of mitogen-activated protein kinase (MAPK) and NF-κB within an hour of infection, heat-killed bacteria did not show any inhibitory effect on the MAPK and NF-κB signaling pathways. Knockdown of Toll-like receptor 2 (TLR2) via RNA interference abolished the suppressive effect of T. denticola on the expression of HBD-3. Heat-killed T. denticola but not live bacteria could activate TLR2 in CHO/CD14/TLR2 reporter cells, suggesting that T. denticola contains a heat-labile inhibitor(s) of TLR2 in addition to ligands recognized by TLR2. Indeed, live T. denticola was able to inhibit TLR2 activation by Pam3CSK. In conclusion, T. denticola suppressed the expression of HBD-3 by inhibiting the TLR2 axis in gingival epithelial cells. These results may provide new insight into the pathogenesis of periodontitis caused by T. denticola.

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

2007 ◽  
Vol 53 (11) ◽  
pp. 1232-1238 ◽  
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.

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.

Sign in / Sign up

Export Citation Format

Share Document