scholarly journals Regulation of the Peptidoglycan Amidase PGLYRP2 in Epithelial Cells by Interleukin-36γ

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Glen M. Scholz ◽  
Jacqueline E. Heath ◽  
Jiamin Aw ◽  
Eric C. Reynolds
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Bacterial Pathogen ◽  
Oral Bacteria ◽  
Oral Epithelium ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Mitogen Activated Protein ◽  
Mucosal Homeostasis ◽  
Oral Epithelial

ABSTRACT Interleukin-36 (IL-36) cytokines are important regulators of mucosal homeostasis and inflammation. We have previously established that oral epithelial cells upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis. Here, we have established that IL-36γ can stimulate the gene expression of mechanistically distinct antimicrobial proteins, including the peptidoglycan amidase PGLYRP2, in oral epithelial cells (e.g., TIGK cells). PGLYRP2 gene expression was not stimulated by either IL-17 or IL-22, thus demonstrating selectivity in the regulation of PGLYRP2 by IL-36γ. The IL-36γ-inducible expression of PGLYRP2 was shown to be mediated by IRAK1- and p38 mitogen-activated protein (MAP) kinase-dependent signaling. Furthermore, our finding that IL-36γ-inducible PGLYRP2 expression was reduced in proliferating TIGK cells but increased in terminally differentiating cells suggests that control of PGLYRP2 expression is associated with the maturation of the oral epithelium. PGLYRP2 expression in TIGK cells can also be directly stimulated by oral bacteria. However, the extracellular gingipain proteases (Kgp and RgpA/B) produced by P. gingivalis, which are critical virulence factors, can antagonize PGLYRP2 expression. Thus, the expression of IL-36γ by oral epithelial cells in response to P. gingivalis might enable the subsequent autocrine stimulation of PGLYRP2 expression. In summary, our data identify how IL-36γ may promote oral mucosal homeostasis by regulating PGLYRP2 expression.

Synergism between TLRs and NOD1/2 in Oral Epithelial Cells

2008 ◽  
Vol 87 (7) ◽  
pp. 682-686 ◽  
Author(s):  
A. Uehara ◽  
H. Takada
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Oral Bacteria ◽  
Innate Immune ◽  
Oral Epithelium ◽  
Innate Immune Responses ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Pro Inflammatory Cytokines

Oral epithelium is the first barrier against oral bacteria in periodontal tissue. Oral epithelial cells constitutively express Toll-like receptors (TLRs) and NOD1/2, functional receptors which induce the production of antibacterial factors such as peptidoglycan recognition proteins (PGRPs) and β-defensin 2, but not pro-inflammatory cytokines such as interleukin (IL)-8. In this study, we hypothesized that innate immune responses in the oral epithelium are enhanced in inflamed tissue. We found that NOD1 and NOD2 agonists, in combination with TLR agonists, synergistically induced production of PGRPs and of β-defensin 2 in human oral epithelial cells via NF-κB. In contrast, co-stimulation with NOD1/2 and TLR ligands had no effect on the production of pro-inflammatory cytokines (IL-6, IL-8, and monocyte chemoattractant protein-1). These findings indicate that, in innate immune responses to invading microbes, a combination of signaling through TLRs and NODs leads to the synergistic activation of antibacterial responses in the oral epithelium.

Toll-like Receptors, NOD1, and NOD2 in Oral Epithelial Cells

2006 ◽  
Vol 85 (6) ◽  
pp. 524-529 ◽  
Author(s):  
Y. Sugawara ◽  
A. Uehara ◽  
Y. Fujimoto ◽  
S. Kusumoto ◽  
K. Fukase ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Host Defense ◽  
Inflammatory Responses ◽  
Immunohistochemical Analysis ◽  
Oral Bacteria ◽  
Innate Immune ◽  
Oral Epithelium ◽  
Toll Like Receptor ◽  
Oral Epithelial Cells ◽  
Oral Epithelial

Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that oral epithelium is endowed with innate immune receptors for bacterial components, which play roles in host defense against bacterial infection without being accompanied by excessive inflammatory responses. We found clear expression of Toll-like receptor (TLR)4 as well as TLR2, and strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. We also showed that primary oral epithelial cells in culture expressed these molecules using PCR, flow cytometry, and immunostaining. In inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in healthy tissue. Upon stimulation with synthetic ligands for these receptors, the expression of β-defensin 2 was markedly up-regulated. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses.

scholarly journals Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

2015 ◽  
Vol 83 (7) ◽  
pp. 2614-2626 ◽  
Author(s):  
Rohitashw Kumar ◽  
Darpan Saraswat ◽  
Swetha Tati ◽  
Mira Edgerton
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Oral Candidiasis ◽  
Oral Microbiome ◽  
Proteinase Activity ◽  
Adhesion Properties ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Cell Cell

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually withC. albicanscells overexpressing Sap6 (SAP6OE and a Δsap8strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6strain was attenuated. These hypervirulent strains had highly aggregative colony structurein vitroand higher secreted proteinase activity; however, the levels of proteinase activity ofC. albicansSaps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6OE and Δsap8cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increasedC. albicansadhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

Pro-inflammatory Cytokines Up-regulate MUC1 Gene Expression in Oral Epithelial Cells

2003 ◽  
Vol 82 (11) ◽  
pp. 883-887 ◽  
Author(s):  
X. Li ◽  
L. Wang ◽  
D.P. Nunes ◽  
R.F. Troxler ◽  
G.D. Offner
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Oral Epithelial Cells ◽  
Muc1 Gene ◽  
Oral Epithelial ◽  
Pro Inflammatory Cytokines

scholarly journals Augmentation of Epithelial Resistance to Invading Bacteria by Using mRNA Transfections

2013 ◽  
Vol 81 (11) ◽  
pp. 3975-3983 ◽  
Author(s):  
Xianqiong Zou ◽  
Brent S. Sorenson ◽  
Karen F. Ross ◽  
Mark C. Herzberg
Keyword(s):  
Epithelial Cells ◽  
Open Reading Frames ◽  
Antimicrobial Protein ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Content Type ◽  
Protein Levels ◽  
Oral Epithelial Cells ◽  
Mrna Transfection ◽  
Oral Epithelial

ABSTRACTTo protect against invading bacteria, oral epithelial cells appear to use two effector antimicrobial peptides (AMPs): calprotectin (S100A8-S100A9 heterodimer [S100A8/A9]) in the cytosol and cathelicidin antimicrobial protein (CAMP) in endosomes. We sought to learn whether innate immunity might be augmented benignly to increase resistance against invasive bacteria. Epithelial cells were transiently transfected with mRNA constructs containing either theCAMP,S100A8, andS100A9open reading frames,A8-IRES-A9(fusion sequence), orA8-nIRES-A9(fusion with native internal ribosome entry site [IRES] sequence). CAMP, S100A8, and S100A9 protein levels generally peaked between 16 and 44 h after mRNA transfection, depending on the construct; CAMP was processed to LL-37 over time. Following transfection with the respective mRNAs, CAMP and S100A8/A9 each independently increased resistance of epithelial cells to invasion byListeriaandSalmonellafor up to 48 h; tandem S100A8/A9 constructs were also effective. Cotransfection to express S100A8/A9 and CAMP together augmented resistance, but synergy was not seen. Independent of the new proteins produced, transfection reduced cell viability after 48 h by 20%, with only 2% attributable to apoptosis. Taken together, these results suggest that epithelial cell resistance to invasive pathogens can be augmented by transient transfection of antimicrobial mRNAs into epithelial cells.

scholarly journals The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Norma V. Solis ◽  
Marc Swidergall ◽  
Vincent M. Bruno ◽  
Sarah L. Gaffen ◽  
Scott G. Filler
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Oral Epithelium ◽  
New Approach ◽  
Oral Epithelial Cells ◽  
Aryl Hydrocarbon ◽  
Molecule Inhibitor ◽  
Oral Epithelial ◽  
Cell Signaling Pathways

ABSTRACT Oropharyngeal candidiasis (OPC), caused predominantly by Candida albicans, is a prevalent infection in patients with advanced AIDS, defects in Th17 immunity, and head and neck cancer. A characteristic feature of OPC is fungal invasion of the oral epithelial cells. One mechanism by which C. albicans hyphae can invade oral epithelial cells is by expressing the Als3 and Ssa1 invasins that interact with the epidermal growth factor receptor (EGFR) on epithelial cells and stimulate endocytosis of the organism. However, the signaling pathways that function downstream of EGFR and mediate C. albicans endocytosis are poorly defined. Here, we report that C. albicans infection activates the aryl hydrocarbon receptor (AhR), leading to activation of Src family kinases (SFKs), which in turn phosphorylate EGFR and induce endocytosis of the fungus. Furthermore, treatment of oral epithelial cells with interferon gamma inhibits fungal endocytosis by inducing the synthesis of kynurenines, which cause prolonged activation of AhR and SFKs, thereby interfering with C. albicans-induced EGFR signaling. Treatment of both immunosuppressed and immunocompetent mice with an AhR inhibitor decreases phosphorylation of SFKs and EGFR in the oral mucosa, reduces fungal invasion, and lessens the severity of OPC. Thus, our data indicate that AhR plays a central role in governing the pathogenic interactions of C. albicans with oral epithelial cells during OPC and suggest that this receptor is a potential therapeutic target. IMPORTANCE OPC is caused predominantly by the fungus C. albicans, which can invade the oral epithelium by several mechanisms. One of these mechanisms is induced endocytosis, which is stimulated when fungal invasins bind to epithelial cell receptors such as EGFR. Receptor binding causes rearrangement of epithelial cell microfilaments, leading to the formation of pseudopods that engulf the fungus and pull it into the epithelial cell. We discovered AhR acts via SFKs to phosphorylate EGFR and induce the endocytosis of C. albicans. Our finding that a small molecule inhibitor of AhR ameliorates OPC in mice suggests that a strategy of targeting host cell signaling pathways that govern epithelial cell endocytosis of C. albicans holds promise as a new approach to preventing or treating OPC. IMPORTANCE OPC is caused predominantly by the fungus C. albicans, which can invade the oral epithelium by several mechanisms. One of these mechanisms is induced endocytosis, which is stimulated when fungal invasins bind to epithelial cell receptors such as EGFR. Receptor binding causes rearrangement of epithelial cell microfilaments, leading to the formation of pseudopods that engulf the fungus and pull it into the epithelial cell. We discovered AhR acts via SFKs to phosphorylate EGFR and induce the endocytosis of C. albicans. Our finding that a small molecule inhibitor of AhR ameliorates OPC in mice suggests that a strategy of targeting host cell signaling pathways that govern epithelial cell endocytosis of C. albicans holds promise as a new approach to preventing or treating OPC.

scholarly journals The Influence of Oral Bacteria on Epithelial Cell MigrationIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Alexa M. G. A. Laheij ◽  
Johannes J. de Soet ◽  
Enno C. I. Veerman ◽  
Jan G. M. Bolscher ◽  
Cor van Loveren
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Oral Bacteria ◽  
Bacterial Cells ◽  
Oral Epithelial Cells ◽  
Prevotella Nigrescens ◽  
Hematopoetic Stem Cell ◽  
Oral Epithelial ◽  
Hematopoetic Stem Cell Transplantation

Oral ulcerations often arise as a side effect from chemo- and radiation therapy. In a previous clinical study,Porphyromonas gingivaliswas identified as a positive predictor for oral ulcerations after hematopoetic stem cell transplantation, possibly incriminatingP. gingivalisin delayed healing of the ulcerations. Therefore, it was tested whetherP. gingivalisand its secreted products could inhibit the migration of oral epithelial cells in anin vitroscratch assay. To compare, the oral bacteriaPrevotella nigrescens,Prevotella intermedia,Tannerella forsythia, andStreptococcus mitiswere included. A standardized scratch was made in a confluent layer of human oral epithelial cells. The epithelial cells were challenged with bacterial cells and with medium containing secretions of these bacteria. Closure of the scratch was measured after 17 h using a phase contrast microscope.P. gingivalis,P. nigrescens, and secretions ofP. gingivalisstrongly inhibited cell migration. A challenge with 1000 heat-killed bacteria versus 1 epithelial cell resulted in a relative closure of the scratch of 25% forP. gingivalisand 20% forP. nigrescens. Weaker inhibitory effects were found for the other bacteria. The results confirmed our hypothesis that the oral bacteria may be involved in delayed wound healing.

scholarly journals Behaviour of Human Oral Epithelial Cells Grown on Invisalign® SmartTrack® Material

Materials ◽  
2020 ◽  
Vol 13 (23) ◽  
pp. 5311
Author(s):  
Michael Nemec ◽  
Hans Magnus Bartholomaeus ◽  
Michael H. Bertl ◽  
Christian Behm ◽  
Hassan Ali Shokoohi-Tabrizi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Inflammatory Markers ◽  
Cell Counting ◽  
Optical Cell ◽  
Epithelial Barrier Function ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
The Impact

Invisalign aligners have been widely used to correct malocclusions, but their effect on oral cells is poorly known. Previous research evaluated the impact of aligners’ eluates on various cells, but the cell behavior in direct contact with aligners is not yet studied. In the present study, we seeded oral epithelial cells (cell line Ca9-22) directly on Invisalign SmartTrack material. This material is composed of polyurethane and co-polyester and exhibit better mechanical characteristics compared to the predecessor. Cell morphology and behavior were investigated by scanning electron microscopy and an optical cell moves analyzer. The effect of aligners on cell proliferation/viability was assessed by cell-counting kit (CCK)-8 and 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and live/dead staining. The expression of inflammatory markers and proteins involved in epithelial barrier function was measured by qPCR. Cells formed cluster-like structures on aligners. The proliferation/viability of cells growing on aligners was significantly lower (p < 0.05) compared to those growing on tissue culture plastic (TCP). Live/dead staining revealed a rare occurrence of dead cells on aligners. The gene expression level of all inflammatory markers in cells grown on aligners’ surfaces was significantly increased (p < 0.05) compared to cells grown on TCP after two days. Gene expression levels of the proteins involved in barrier function significantly increased (p < 0.05) on aligners’ surfaces after two and seven days of culture. Aligners’ material exhibits no cytotoxic effect on oral epithelial cells, but alters their behavior and the expression of proteins involved in the inflammatory response, and barrier function. The clinical relevance of these effects has still to be established.

scholarly journals Reduced Salivary Mucin Binding and Glycosylation in Older Adults Influences Taste in an In Vitro Cell Model

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2280 ◽  
Author(s):  
Rose-Anna G. Pushpass ◽  
Nicola Pellicciotta ◽  
Charles Kelly ◽  
Gordon Proctor ◽  
Guy H. Carpenter
Keyword(s):  
Older Adults ◽  
Epithelial Cells ◽  
Taste Receptor ◽  
Receptor Activation ◽  
Oral Epithelium ◽  
Younger Adults ◽  
Oral Epithelial Cells ◽  
Salivary Mucin ◽  
Oral Epithelial

Background: Taste loss is a significant problem in older adults, affecting quality of life and nutrition. Altered salivary rheology and loss of mucin function may contribute to taste loss by reducing mucosal defences in the oral cavity, impairing sensitivity to oral stimulants. This study aimed to investigate the effects of salivary rheology on taste loss in ageing. Salivary mucin glycosylation and binding to the oral epithelium was investigated in older and younger adults. A cell-based model was utilised to consider the role of saliva in taste loss. Methods: Human subjects aged >60 years (n = 25) and 18–30 (n = 30) provided saliva samples which were analysed for viscosity, mucin composition and mucin binding to oral epithelial cells (TR146/MUC1). Oral epithelial cells (TR146/MUC1 and SCC090) provided models for taste receptor activation. Results: Reduced levels and sialylation of MUC7 were evident in saliva of older adults which may lead to reduced viscoelasticity, while viscosity is unaffected. Impaired muco-adhesion of saliva from older adults was also observed. Saliva from older adults facilitated the bitter taste receptor activation less well than saliva from younger adults. The causes of taste dysfunction in older adults are unknown, but this study supports a role of saliva in facilitating the activation of taste receptors.

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