interleukin-8 and Dental-Caries

Recent advances in immunology have disclosed the enormous complexity of the immune regulatory system. The dental pulp is equipped to mount adaptive immune responses to caries, which include at least antigen-presenting cells, lymphocytes, mast cells and their cytokines, and chemokines. The purpose of this review is to summarize our current understanding of the roles of these cellular and molecular components in the irreversibly inflamed pulp. The immunopathology of abscess formation and the mechanisms for painless pulpitis are also discussed.

Topics: Animals; B-Lymphocytes; Chemokines; Cytokines; Dendritic Cells; Dental Caries; Dental Pulp; Humans; Immunity, Innate; Interleukin-8; Macrophages; Periapical Abscess; Pulpitis; T-Lymphocytes; Toothache

Dental caries or trauma can expose human dental pulp cells (DPCs) to various oral microorganisms, which play an important role in the development of an innate immune response. In the present study, we examined the expression of Toll-like receptors (TLRs) for sensing microbe-associated molecular patterns in human DPCs. Interestingly, real-time PCR analysis demonstrated that TLR3 is the most highly expressed among 10 different TLRs in human DPCs. Poly(I:C), a representative TLR3 ligand mimicking viral double-stranded RNA, potently induced IL-8 expression in a time- and dose-dependent manner. Concordantly, poly(I:C) treatment substantially increased the expression of pro-inflammatory cytokines and chemokines such as IL-6, CCL2, and CXCL10. Human DPCs transfected with TLR3 siRNA exhibited decreased IL-8 production compared with non-targeting siRNA-transfected cells, suggesting that the expression of poly(I:C)-induced inflammatory cytokines is dependent on TLR3. IL-8 secretion induced by poly(I:C) was down-regulated by MAP kinase inhibitors, indicating that the MAP kinase pathway contributes to IL-8 production. Furthermore, C/EBPβ and NF-κB were essential transcriptional factors for poly(I:C)-induced IL-8 expression, as demonstrated by the transient transfection and reporter gene assay. Since lipoproteins are known as major immunostimulatory components of bacteria, human DPCs were treated with poly(I:C) together with Pam2CSK4, a synthetic lipopeptide mimicking bacterial lipoproteins. Pam2CSK4 and poly(I:C) co-treatment synergistically increased IL-8 production in comparison to Pam2CSK4 or poly(I:C) alone, implying that co-infection of viruses and bacteria can synergistically induce inflammatory responses in the dental pulp. Taken together, these results suggest that human DPCs potentially sense and respond to viral double-stranded RNAs, leading to effective induction of innate immune responses.

Topics: Cells, Cultured; Cytokines; Dental Caries; Dental Pulp; Humans; Immunity, Innate; Interleukin-8; Poly I-C; RNA, Double-Stranded; RNA, Small Interfering; Toll-Like Receptor 3; Toll-Like Receptors

Staphylococcus epidermidis is one of most prevalent in dental caries or dental pulp which has the capability of horizontal genetic transfer between different bacterial species in the oropharynx, suggesting that it may evolve with the dissemination of resistant determinants, This study was performed to molecularly characterize and differentiate S. epidermidis isolated from dental caries and healthy individual. Also, two important cytokines in inflammation were assayed caused due to S. epidermidis of health and dental caries sources. Dental caries strains were more resistant with high MIC

Topics: Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Cytokines; Dental Caries; Dental Pulp; Dental Pulp Cavity; Drug Resistance, Multiple, Bacterial; Fibroblasts; Humans; Immunohistochemistry; Inflammation; Interleukin-1beta; Interleukin-8; Interleukins; Microbial Sensitivity Tests; Molecular Epidemiology; Oropharynx; Staphylococcus epidermidis; Virulence; Virulence Factors

Dental caries is the most common microbial disease affecting mankind. Caries risk assessment methods, identification of biomarkers and vaccine development strategies are being emphasized to control the incidence of the largely preventable disease. Pattern recognition receptors such as the toll like receptors (TLR) have been implicated as modulators of host-microbial interactions. Soluble TLR-2 and its co-receptor, CD14 identified in saliva can bind the cell wall components of cariogenic bacteria and modulate the disease process. The objective of this study is to determine the potential of salivary sTLR-2 and sCD14 as biomarkers of caries activity and indirect measures of the cariogenic bacterial burden.. Unstimulated whole saliva was collected from twenty caries free and twenty caries active children between the ages of 5 and 13 years. The concentration of sCD14 and sTLR-2 together with that of the cytokine IL-8 reported to be increased in dental caries was assessed by the enzyme linked immunosorbent assay.. While the level of sCD14 and that of IL-8 was equivocal between the two groups, the sTLR-2 concentration in caries active saliva was significantly higher than that in caries free saliva.. The sTLR-2 in saliva could serve as a potential biomarker for caries activity.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Cohort Studies; Dental Caries; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Lipopolysaccharide Receptors; Male; Non-Randomized Controlled Trials as Topic; Prospective Studies; Saliva; Salivary Proteins and Peptides; Spectrophotometry; Toll-Like Receptor 2

To measure and compare the levels of the cytokines IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γ in pulpal blood from irreversible pulpitis, asymptomatic caries exposure and normal pulps.. Blood was obtained from pulp exposure sites using cotton pellets. Twenty-five samples were obtained from normal teeth, 40 from asymptomatic caries-exposed pulps and 43 from irreversible pulpitis teeth. Cytokine levels were determined by high-sensitivity ELISA. Data were statistically analysed using Kruskal-Wallis and Mann-Whitney U-tests.. Significantly higher levels (P < 0.05) of IL-6, IL-8, IL-10, TNF-α and IFN-γ were detected in caries-exposed pulps and irreversible pulpitis as compared to normal teeth. IL-2 and IL-10 levels were significantly higher (P < 0.05) in caries-exposed pulps as compared to irreversible pulpitis, whilst IL-8 was significantly higher (P < 0.001) in irreversible pulpitis as compared to caries-exposed teeth. Most interestingly, IL-6/IL-10 and IL-8/IL-10 ratios were significantly higher (P < 0.001) in irreversible pulpitis compared with both caries-exposed and normal teeth.. Levels of IL-8 and the ratios of IL-6/IL-10 and IL-8/IL-10 have the potential to be indicators of pulpal inflammation in caries exposure cases. Cytokine estimation in pulpal blood may help in the diagnosis of pulpal inflammation.

Topics: Adolescent; Adult; Biomarkers; Dental Caries; Dental Pulp; Dental Pulp Exposure; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Pulpitis; Tumor Necrosis Factor-alpha; Young Adult

Dental caries is an inflammatory disease with multifactorial etiology. The presented study was conducted to test the hypothesis that the elevation of salivary cytokines - interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor (TNF-a) is changed in dental caries patients. IL-6, IL-8 and TNF-a are particularly relevant to inflammation, one of the very first responses of the host to a pathological insult.. Whole saliva from 26 patients with dental caries, as well as 10 healthy persons, was investigated for the presence of IL-6, IL-8 and TNF-a by enzyme immunoassay - ELISA.. The results showed that an elevation of IL-6, IL-8 and TNF-a in unstimulated whole saliva in subjects with dental caries, compared with controls, increased and was statistically significant in all cases (p <0.05). The study also show a positive correlation between TNF-a and IL-8.. These data suggest links between the production of tumour necrosis factor (TNF-a), interleukin-6 (IL-6), interleukin-8 (IL-8) in saliva and dental caries disease.

Topics: Adolescent; Biomarkers; Dental Caries; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-6; Interleukin-8; Poland; Saliva; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

The aim of this study was to evaluate correlations between levels of cytokines in secreted stimulated saliva in patients with chronic kidney disease (CKD) and hyposalivation.. Seventy patients with clearance <20 mL/min/1.73 m(2) were evaluated; 40 were predialysis, 21 hemodialysis, and 9 peritoneal dialysis, and they were matched with 70 control subjects. Salivary flow rate was measured and submandibular/sublingual saliva collected. Analyses were performed for whole protein content using a protein assay, and levels of tumor necrosis factor (TNF) α, interleukin (IL) 1β, γ-interferon (γ-INF), IL-6, IL-8, IL-10, monocyte chemotactic protein (MCP) 1, and soluble intercellular adhesion molecule (sICAM) 1, by using Luminex technology.. Patients with CKD had lower (P = .03) stimulated salivary secretion rate and higher salivary whole protein concentration (P = .002) than control subjects. Concentrations of IL-8 (P = .03) and MCP-1 (P = .002) were decreased and TNF-α/IL-10 (P = .05) and IL-8/IL10 (P = .03) ratios were decreased in CKD patients. CKD patients with low secretion levels of stimulated saliva expressed decreased levels of TNF-α (P = .04), IL-1β (P = .02), γ-INF (P = .03), IL-6 (P = .003), IL-8 (P = .005), MCP-1 (P = .006), and sICAM-1 (P = .02).. Salivary cytokines and secretion rates are significantly decreased in CKD patients. Further research is necessary to understand operating mechanisms and clinical implications of the down-regulation of inflammatory markers in saliva.

Topics: Case-Control Studies; Chemokine CCL2; Cross-Sectional Studies; Cytokines; Dental Caries; Female; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Periapical Diseases; Periodontitis; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency, Chronic; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sublingual Gland; Submandibular Gland; Tumor Necrosis Factor-alpha; Xerostomia

Odontoblasts (OBs) are cells lining the inner surface of the tooth. Their potential role in host defenses within the tooth is suggested by their production of antimicrobial beta-defensins, but their role needs confirmation. The present study sought to define the roles of human OBs in microbial recognition and innate host responses. Toll-like receptor 2 (TLR2) and TLR4, as well as CCR6, were immunolocalized in human OBs and their dentinal processes in situ. To examine OB function we used organotypic tooth crown cultures to maintain human OBs within their dentin scaffold. Cells in the OB layer of cultured and non-cultured crown preparations expressed mRNA for several markers of innate immunity including chemokine CCL20, chemokine receptor CCR6, TLR2, TLR4 and the OB marker dentin sialophosphoprotein (DSPP). Expression of human beta-defensin 1 (hBD1), hBD2, hBD3, interleukin-8 (IL-8), and CCL20 increased with time in culture. Tooth crown odontoblast (TcOB) cultures were stimulated with agonist that was specific for TLR2 (Pam3CSK4) or TLR4 [Escherichia coli lipopolysaccharide (LPS)]. Nuclear factor-kappaB assays confirmed the TLR2 activity of Pam3CSK4 and the TLR4 activity of LPS. LPS up-regulated IL-1beta, tumor necrosis factor-alpha (TNF-alpha), CCL20, hBD2, IL-8, TLR2 and TLR4; however, Pam3CSK4 down-regulated these mRNAs. IL-1beta, TNF-alpha, CCL20 were also up-regulated from six-fold to 30-fold in TcOB preparations from decayed teeth. Our results show for the first time that OBs express microbial pattern recognition receptors in situ, thus allowing differential responses to gram-positive and gram-negative bacteria, and suggest that pro-inflammatory cytokines and innate immune responses in decayed teeth may result from TLR4 signaling.

Topics: Antigen-Presenting Cells; beta-Defensins; Chemokine CCL20; Chemokines, CC; Dental Caries; Dentin; Extracellular Matrix Proteins; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-8; Lipopeptides; Lipopolysaccharides; Macrophage Inflammatory Proteins; Odontoblasts; Organ Culture Techniques; Peptides; Phosphoproteins; Receptors, CCR6; Receptors, Chemokine; Sialoglycoproteins; Toll-Like Receptor 2; Toll-Like Receptor 4; Tooth Crown; Tumor Necrosis Factor-alpha

Streptococcus mutans possesses different cell wall molecules, such as protein of the I/II family, the serotype f polysaccharide rhamnose glucose polymer (RGP), and lipoteichoic acid (LTA), which act as adhesins and modulins, allowing S. mutans to colonize teeth and cause dental caries and pulpitis. We tested several isogenic mutants of S. mutans defective in protein I/II and/or RGP, as well as purified modulins such as protein I/II, RGP, and LTA, for their binding and activation abilities on monocytic, dental pulp (DP), and periodontal ligament (PDL) cells. Our results demonstrate that both protein I/II and RGP play important roles in streptococcal adherence to human monocytic and fibroblastic cells, whereas LTA is only a minor adhesin. In the activation process, the cytokine response elicited is polarized toward a Th1 response which seems principally due to protein I/II and RGP. Even if protein I/II seems to be more efficient in its purified form in triggering cells to release interleukin-8 (IL-8), RGP is the most efficient cytokine-stimulating component in intact bacteria, while LTA plays only a minor role. In cell activation, we showed, by using either cytochalasin D or coated ligands, that internalization of either S. mutans, S. mutans isogenic mutants, or purified ligands is not necessary to trigger cells to release IL-8. We also showed that, besides the implication of monocytes in pulpal inflammation, fibroblast-like cells such as DP and PDL cells are also actively implicated in local inflammation and in the generation of a Th1 response after stimulation with S. mutans cells or antigens.

Topics: Adhesins, Bacterial; Bacterial Adhesion; Bacterial Proteins; Cell Line; Dental Caries; Dental Pulp; Genes, Bacterial; Humans; Hydro-Lyases; Interleukin-6; Interleukin-8; Membrane Glycoproteins; Monocytes; Mutagenesis, Insertional; Periodontal Ligament; Streptococcal Infections; Streptococcus mutans; Tumor Necrosis Factor-alpha