Inhibitors of collagenolytic enzymes synthesized by fibroblasts and epithelial cells from porcine and macaque 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.

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HORMONE-ASSOCIATED METABOLIC DISORDERS OF THE ORAL CAVITY ORGANS IN WOMEN OF REPRODUCTIVE AGE

PROBLEMS OF ENDOCRINE PATHOLOGY ◽

10.21856/j-pep.2021.4.17 ◽

2021 ◽

Vol 78 (4) ◽

pp. 127-134

Author(s):

George Khodorovskyi ◽

Lyubov Panina ◽

Tetiana Shchurko

Keyword(s):

Epithelial Cells ◽

Oral Cavity ◽

Steroid Hormones ◽

Tight Junctions ◽

Sex Hormones ◽

Reproductive System ◽

Periodontal Ligament ◽

Sex Steroid Hormones ◽

Sex Steroid ◽

Periodontal Tissues

There is emerging evidence of a possible relationship between the oral cavity and reproductive organs. Recent studies suggest these functional relations. The aim of this review was to synthesize the available evidence on this relationship. Clinical observation established that sex hormones enhance gingival inflammation in periodontal healthy women during pregnancy and that periodontal condition is associated with variation of sex hormones in blood. Estrogen regulates DNA synthesis in human gingival epithelial cells and periodontal ligament, estrogen reduces down regulation of cytokines. Estrogen and progesterone affect the periodontium via appropriate receptors (estrogen receptor and progesterone receptor). They are localized in human periodontium, demonstrating that periodontal tissues are the target tissues for these hormones. Testosterone receptors are found in the periodontal tissues. It inhibits prostaglandin secretion and reduces interleukin production. At the same time testosterone stimulates osteoblast proliferation and differentiation, also enhances matrix synthesis by fibroblast, osteoblasts, and periodontal ligament. The role of testosterone in the formation of teeth is demonstrated in the paper. In females and males, in saliva there are sex steroid hormones. The study examined the entry mode of hormones into saliva. The results suggest that lipid soluble unconjugated steroids (estriol, testosterone, progesterone) enter saliva via intracellular route; the conjugated steroids (lipid insoluble (dehydroepiandrosterone, conjugated estrogens)) enter via the ‘tight junctions’ (infiltrations through the tight junctions between the acinar cells). Recent evidence indicates that organs of the oral cavity (salivary glands, periodontal tissues, oral epithelial cells mucus) produce ghrelin-hormone which affects organs of the reproductive system directly or indirectly via hypothalamic-pituitary-gonadal axis. In all these organs, there is an appropriate receptor. In conclusion, the organs of oral cavity and organs of reproductive system are functionally linked by sex steroid hormones and ghrelin, besides that periodont can influence ovaries by neuro-reflectory link.

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In Vitro Homeostasis of Rat Oral Epithelial Cell Cultures Following Withdrawal of Periodontal Pathogens

Brazilian Dental Journal ◽

10.1590/0103-6440202002561 ◽

2020 ◽

Vol 31 (2) ◽

pp. 135-142

Author(s):

Ali A Abdulkareem ◽

Hayder R Abdulbaqi ◽

Michael R Milward

Keyword(s):

Epithelial Cells ◽

Barrier Function ◽

Inflammatory Markers ◽

Tissue Inhibitor Of Metalloproteinase ◽

Epithelial Barrier ◽

Oral Keratinocytes ◽

Periodontal Pathogens ◽

Epithelial Barrier Function ◽

Periodontal Tissues

Abstract Inflammation of periodontal tissues is the consequence of interaction between periodontal pathogens and immune system. This is associated with increased expression of inflammatory cytokines, which may exert destructive effect to the periodontal tissues when released over long period. The aim of this study was to chronologically track the homeostasis of oral keratinocytes following removal of periodontal pathogens. This was done by investigating expression of selected inflammatory markers and integrity of epithelial monolayers in vitro. Rat oral keratinocytes were stimulated with heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis over 7-days then bacteria were washed away and epithelial cells re-cultured for 3-days. Expression of IL-1β, IL-6, and IL-8 was measured by ELISA while transcription of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase -8 (MMP-8) was measured by polymerase chain reaction before and after removal of bacteria. Integrity of epithelial sheet was investigated by using transepithelial electrical resistance. Data showed general downregulation of IL-1b, IL-6, and IL-8 associated with restoring transcription of TIMP-1 and MMP-8 to normal level following removal of bacteria from epithelial cultures. However, expression of IL-8 and MMP-8 remained significantly higher than unstimulated epithelial cells despite withdrawal of F. nucleatum and P. gingivalis respectively from oral keratinocytes cultures. In addition, integrity of epithelial barrier function remained compromised even after removal of P. gingivalis. Results suggest that even after three days following removal of periodontal pathogens, oral keratinocytes sustained persistent upregulation of certain inflammatory markers that could compromise integrity of epithelial barrier function.

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Proteolysis of ICAM-1 on Human Oral Epithelial Cells by Gingipains

Journal of Dental Research ◽

10.1177/154405910308201007 ◽

2003 ◽

Vol 82 (10) ◽

pp. 796-801 ◽

Cited By ~ 41

Author(s):

H. Tada ◽

S. Sugawara ◽

E. Nemoto ◽

T. Imamura ◽

J. Potempa ◽

...

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Immune Evasion ◽

Intercellular Adhesion Molecule ◽

Dependent Manner ◽

Intercellular Adhesion Molecule 1 ◽

Periodontal Tissues ◽

Oral Epithelial Cells ◽

Oral Epithelial Cell ◽

Oral Epithelial

Cysteine proteinases (gingipains) from Porphyromonas gingivalis are considered key virulence factors of severe periodontitis and host immune evasion. Since expression of intercellular adhesion molecule-1 (ICAM-1) on gingival epithelium is indispensable in polymorphonuclear leukocyte (PMN) migration at the site of periodontitis, we examined the effects of gingipains on the expression of ICAM-1 on human oral epithelial cell lines (KB and HSC-2) by flow cytometry and Western blotting. We found that three purified forms of gingipains efficiently reduced ICAM-1 expression on the cells in a time- and dose-dependent manner. Gingipains reduced the expression on fixed cells and degraded the ICAM-1 in the cell membranes, indicating that the reduction resulted from direct proteolysis. They then disturbed the ICAM-1-dependent adhesion of PMNs to the cells. These results indicate that gingipains cleave ICAM-1 on oral epithelial cells, consequently disrupting PMN-oral epithelial cell interaction, and are involved in immune evasion by the bacterium in periodontal tissues.

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

Pathogens ◽

10.3390/pathogens9040248 ◽

2020 ◽

Vol 9 (4) ◽

pp. 248 ◽

Cited By ~ 2

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.

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Suppression of T-Cell Chemokines by Porphyromonas gingivalis

Infection and Immunity ◽

10.1128/iai.00264-13 ◽

2013 ◽

Vol 81 (7) ◽

pp. 2288-2295 ◽

Cited By ~ 36

Author(s):

Catherine E. Jauregui ◽

Qian Wang ◽

Christopher J. Wright ◽

Hiroki Takeuchi ◽

Silvia M. Uriarte ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

Porphyromonas Gingivalis ◽

Mononuclear Cells ◽

Ectopic Expression ◽

Fusobacterium Nucleatum ◽

Peripheral Blood Mononuclear ◽

Content Type ◽

Periodontal Tissues ◽

Interferon Regulatory Factor 1

ABSTRACTPorphyromonas gingivalisis a major pathogen in periodontal disease and is associated with immune dysbiosis. In this study, we found thatP. gingivalisdid not induce the expression of the T-cell chemokine IP-10 (CXCL10) from neutrophils, peripheral blood mononuclear cells (PBMCs), or gingival epithelial cells. Furthermore,P. gingivalissuppressed gamma interferon (IFN-γ)-stimulated release of IP-10, ITAC (CXCL11), and Mig (CXCL9) from epithelial cells and inhibited IP-10 secretion in a mixed infection with the otherwise stimulatoryFusobacterium nucleatum. Inhibition of chemokine expression occurred at the level of gene transcription and was associated with downregulation of interferon regulatory factor 1 (IRF-1) and decreased levels of Stat1. Ectopic expression of IRF-1 in epithelial cells relievedP. gingivalis-induced inhibition of IP-10 release. Direct contact betweenP. gingivalisand epithelial cells was not required for IP-10 inhibition. These results highlight the immune-disruptive potential ofP. gingivalis. Suppression of IP-10 and other Th1-biasing chemokines byP. gingivalismay perturb the balance of protective and destructive immunity in the periodontal tissues and facilitate the pathogenicity of oral microbial communities.

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Magnolia officinalis L. Fortified Gum Improves Resistance of Oral Epithelial Cells Against Inflammation

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500658 ◽

2016 ◽

Vol 44 (06) ◽

pp. 1167-1185 ◽

Cited By ~ 3

Author(s):

Jessica Walker ◽

Julia Maria Imboeck ◽

Joel Michael Walker ◽

Amarnath Maitra ◽

Hady Haririan ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Ex Vivo ◽

Chewing Gum ◽

Periodontal Tissues ◽

Oral Epithelial Cells ◽

Regular Control ◽

Anti Inflammatory ◽

Magnolia Officinalis ◽

Oral Epithelial

Inflammatory diseases of the periodontal tissues are known health problems worldwide. Therefore, anti-inflammatory active compounds are used in oral care products to reduce long-term inflammation. In addition to inducing inflammation, pathogen attack leads to an increased production of reactive oxygen species (ROS), which may lead to oxidative damage of macromolecules. Magnolia officinalis L. bark extract (MBE) has been shown to possess antioxidant and anti-inflammatory potential in vitro. In the present study, the influence of MBE-fortified chewing gum on the resistance against lipopolysaccharide (LPS)-induced inflammation and oxidative stress of oral epithelial cells was investigated in a four-armed parallel designed human intervention trial with 40 healthy volunteers. Ex vivo stimulation of oral epithelial cells with LPS from Porphyromonas gingivalis for 6[Formula: see text]h increased the mRNA expression and release of the pro-inflammatory cytokines IL-1[Formula: see text], IL-[Formula: see text], IL-8, MIP-1[Formula: see text], and TNF[Formula: see text]. Chewing MBE-fortified gum for 10[Formula: see text]min reduced the ex vivo LPS-induced increase of IL-8 release by 43.8 [Formula: see text] 17.1% at the beginning of the intervention. In addition, after the two-week intervention with MBE-fortified chewing gum, LPS-stimulated TNF[Formula: see text] release was attenuated by 73.4 [Formula: see text] 12.0% compared to chewing regular control gum. This increased resistance against LPS-induced inflammation suggests that MBE possesses anti-inflammatory activity in vivo when added to chewing gum. In contrast, the conditions used to stimulate an immune response of oral epithelial cells failed to induce oxidative stress, measured by catalase activity, or oxidative DNA damage.

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Biphasic Functions of Sodium Fluoride (NaF) in Soft and in Hard Periodontal Tissues

International Journal of Molecular Sciences ◽

10.3390/ijms23020962 ◽

2022 ◽

Vol 23 (2) ◽

pp. 962

Author(s):

Xingzhi Wang ◽

Nitesh Tewari ◽

Fuyuki Sato ◽

Keiji Tanimoto ◽

Lakshmi Thangavelu ◽

...

Keyword(s):

Epithelial Cells ◽

Sodium Fluoride ◽

Clinical Applications ◽

Fluoride Treatment ◽

Periodontal Tissues ◽

Low Concentrations ◽

Different Tissues

Sodium fluoride (NaF) is widely used in clinical dentistry. However, the administration of high or low concentrations of NaF has various functions in different tissues. Understanding the mechanisms of the different effects of NaF will help to optimize its use in clinical applications. Studies of NaF and epithelial cells, osteoblasts, osteoclasts, and periodontal cells have suggested the significant roles of fluoride treatment. In this review, we summarize recent studies on the biphasic functions of NaF that are related to both soft and hard periodontal tissues, multiple diseases, and clinical dentistry.

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INFLUENCE OF AGE ON PERIODONTAL HUMAN HEALTH

The actual problems in dentistry ◽

10.18481/2077-7566-2020-16-3-30-36 ◽

2020 ◽

Vol 16 (3) ◽

pp. 30-36

Author(s):

Elena Semencova ◽

Vladimir Bazarnyy ◽

Yuliya Mandra ◽

Larisa Polushina ◽

Elena Svetlakova

Keyword(s):

Epithelial Cells ◽

Inflammatory Process ◽

Periodontal Diseases ◽

Age Groups ◽

Cellular Damage ◽

Periodontal Tissues ◽

Buccal Epithelial Cells ◽

Inflammatory Processes ◽

Somatic Diseases ◽

Study Participants

Subject. With increasing age of patients, in many cases, the severity of periodontal diseases also increases, and dystrophic ones join the inflammatory processes. Local predisposing factors in the oral cavity are aggravated by concomitant somatic diseases and a decrease in compensatory processes against the background of physiological aging. Literature data indicate that the manifestations of the physiological process of aging and pathological processes (inflammatory and dystrophic) can be clearly observed on the example of buccal epithelial cells. The aim is to identify the relationship between the age of patients, their periodontal status and the cytological characteristics of buccal epithelial cells. Methodology. All study participants were divided into two groups: the first included patients with a conditionally healthy periodontium (72 people), the second - with a chronic inflammatory process in the periodontium (57 people). In accordance with the WHO classification, a gradation of age was carried out: young (18―44 years old), mature (45―59 years old), elderly (60―74 years old), senile (75―90 years old). All patients underwent a comprehensive dental examination, sampling and cytological examination of the buccal epithelium, calculation of the integral indices of the buccal cytogram. Results. In healthy patients, a weak positive correlation was established between the cytogenetic index, the index of the accumulation of cytogenetic disorders and age, a weak negative correlation was found between the proliferative index and age. In patients with an inflammatory process in the periodontal tissues, a multidirectional change in the values of the buccal cytogram indices was observed, which may indicate an imbalance in the processes of regeneration, apoptosis, and cellular damage in inflammatory periodontal diseases in older age groups. Conclusions. In patients with healthy periodontal disease, a regular accumulation of cytogenetic disorders occurs with increasing age, while proliferative activity, on the contrary, decreases. Patients with inflammatory phenomena in the periodontal tissues are characterized by imbalance, impaired coordination of regeneration and apoptosis processes, combined with the most pronounced reactivity in the middle age period.

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Interleukin-6 (IL-6) and IL-8 Are Induced in Human Oral Epithelial Cells in Response to Exposure to PeriodontopathicEikenella corrodens

Infection and Immunity ◽

10.1128/iai.67.1.384-394.1999 ◽

1999 ◽

Vol 67 (1) ◽

pp. 384-394 ◽

Cited By ~ 53

Author(s):

Hiromichi Yumoto ◽

Hideaki Nakae ◽

Keiko Fujinaka ◽

Shigeyuki Ebisu ◽

Takashi Matsuo

Keyword(s):

Epithelial Cells ◽

Bacterial Colonization ◽

Enzyme Linked Immunosorbent Assay ◽

Mrna Levels ◽

Kb Cells ◽

Protein Levels ◽

Periodontal Tissues ◽

Oral Epithelial Cells ◽

Oral Epithelial ◽

Stimulation Of

ABSTRACT Periodontitis is the inflammatory response in periodontal tissues elicited by bacterial colonization in periodontal pockets. In this response, pocket epithelial cells are the first cells to come into contact with bacteria. To elucidate this mechanism, we determined the adherence of the periodontopathic bacterium Eikenella corrodens 1073, which has a GalNAc-sensitive lectin-like adhesin (EcLS), to a human oral epithelial carcinoma cell line (KB) and the induction of proinflammatory cytokine production in the cells following exposure to this bacterium in vitro. In the adherence assay, EcLS played a role as the adhesin of this bacterium in adherence to KB cells. In a reverse transcriptase PCR, significant interleukin-8 (IL-8) and IL-6 mRNA levels were induced in response to exposure to this bacterium. In an enzyme-linked immunosorbent assay after an 8-h bacterial exposure, the IL-8 and IL-6 protein levels were 13.5- and 8.3-fold higher than those in the nonexposed controls, respectively. These protein responses were time dependent. Interestingly, whenE. corrodens was separated from KB cells by cell culture inserts, a slight stimulation of the IL-6 and IL-8 mRNA and secreted protein levels was seen. These results imply that the direct contact ofE. corrodens 1073 with oral epithelial cells is not necessarily required for the stimulation of IL-6 and IL-8 secretion. We suggest that E. corrodens induces the epithelial cells to secrete proinflammatory cytokines which serve as an early signaling system to host immune and inflammatory cells in underlying connective tissues.

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