2Department of Biomedical Science, School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
3Department of Restorative Dentistry, School of Dentistry, Federal University of Alagoas, Maceio, Alagoas, Brazil
4School of Dentistry, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
Keywords: Cytokines; Endotoxins; Lipoteichoic Acid; Endodontic Infection
Cytokines are small signaling molecules that mediate host responses to infection, inflammation, and trauma. Pro-inflammatory cytokines initiate or enhance systemic inflammation while anti-inflammatory cytokines reduce inflammation and promote healing. Examples of proinflammatory cytokines include IL-1 and TNF-a whereas IL-10 is an important anti-inflammatory cytokine. Some cytokines can have both pro-inflammatory and anti-inflammatory properties such as the IL-6 as it can inhibit TNF-a and IL-1, at the same time activates IL-10. Cytokines work with each other in a homeostatic network regulation to prevent the constant state of inflammation. In endodontic infection; gram-negative bacteria contribute a high percentage of LPS, a primary virulence factor [29-39]. Murakami et al. [29] detected P.endodontalis LPS in 90% of the samples obtained from patients with acute abscesses. LPS is also known as endotoxins, it forms an integral part of cell wall of gram-negative bacteria [40]. The LPS molecule consists of O-antigen, core oligosaccharide, and a glycolipid component named lipid A [30].These endotoxins are released during bacteria multiplication and after cell death [40]. Similarly, LTA is the main virulence factor of gram positive bacteria. It is an amphiphilic molecule consisting of a poly-glycerolphosphate with a complex glycolipids group attached to it [17]. LPS activates mammalian cells by first binding with Lipopolysaccharide Binding Protein (LBP) in the serum. Subsequently, LBP presents LPS to the CD14/TLR4/MD2 receptor complex. This receptor complex is present on cells like-neutrophils, macrophages, dendritic cells and endothelial cells [18,22]. This interaction activates an intracellular signal transduction cascade, resulting in secretion of inflammatory cytokines. Gram positive bacteria trigger similar cascade by mediating ligands through TLR2 instead of TLR4 [5,23].According to Tietzeet al. [31], Gram negative species tend to induce higher levels of TNF-a than IL-8. However, evidences have shown that P. gingivalis is an exception for this presumption as it has similar activity with the gram-positives. This is due to the heterogeneity of the species lipid A molecule
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Ref |
Year |
Author |
Title |
Virulence factor and cytokines |
Conclusion |
1 | 29 |
2001 |
Murakami et al. |
A possible mechanism of maxillofacial abcess formation: involvement of Porphyromonasendodontalis lipopolysaccharide via the expression of inflammatory cytokines |
Porphyromonasendodontalis LPS TNF-a, IL-1β |
LPS of the bacteria is present in the bacterially infected root canal fluid of about 90% of the patients. The ability of LPS to induce cytokines was reduced by incubating the macrophages with antibodies against the bacterial LPS. ELISA showed a significantly high level of TNF-a to be present in the infectious materials. |
2 | 30 |
2001 |
Gutsmann et al. |
Dual Role of LBP in Neutralization of LPS and Enhancement of LPS-Induced Activation of Mononuclear Cells (MNC) |
LPS IL-1,IL-6, TNF-a |
LBP level rises after acute-phase response due to the activation by IL-1 and IL-6. LPSs activate monocytes and macrophages to secrete TNF-a and IL-1, etc. LBP present as a soluble protein and also as a transmembrane protein of MNC. Low concentrations of LBP enhance the LPS-induced activation of MNC, whereas the acute-phase rise in LBP concentrations inhibits LPS-induced cellular stimulation. |
3 | 25 |
2003 |
Telles et al. |
Lipoteichoic Acid Up-regulates VEGF Expression in Macrophages and Pulp Cells |
LTA VEGF |
LTA induced up to a 9-fold increase in VEGF protein expression in macrophages. LTA is sufficient to induce expression of a pro-angiogenic factor. |
4 | 31 |
2006 |
Tietze et al. |
Differences in innate immune responses upon stimulation with gram positive and gram-negative bacteria |
LTA, LPS, TNF-a, IL-8 |
Gram negative species produced higher amounts of TNF-a while gram positive species produced higher amount of IL-8 due to the activation of different TLRs. Purified gram-negative and gram-positive products may not mimic the response to whole pathogen. |
5 | 32 |
2006 |
Durand et al. |
Lipoteichoic Acid Increases TLR and Functional Chemokine Expression while Reducing Dentin Formation in Odontoblasts |
LTA Chemokines CXCL2 |
TLR trigger secretion of pro-inflammatory chemokines and cytokines that activate blood borne inflammatory cells. CCL2 is the key chemokine produced during microbial infection. Chemokines also influence angiogenesis. |
6 | 33 |
2007 |
Adachi et al. |
Caries-related Bacteria and Cytokines Induce CXCL10 in Dental Pulp |
LTA, CXCL10 |
HDPF stimulated with PGN, but not LTA, were able to produce CXCL10. |
7 | 34 |
2008 |
Staquet et al. |
Different Roles of Odontoblasts and Fibroblasts in Immunity |
LTA CXCL2 and CXCL10 |
CXCL2 and CXCL10 were thus increased by LTA only in odontoblast-like cells |
8 | 35 |
2008 |
Baik JE et al. |
Lipoteichoic Acid Partially Contributes to the Inflammatory Responses to Enterococcus faecalis |
LTA, TNF-a |
LTA of E. faecalis stimulate macrophage to produce significant high level of TNF-a and nitric oxide. LTA also stimulate production of inflammatory mediators. LTA stimulate TLR2 but not TLR4. |
9 | 36 |
2009 |
Soden et al. |
Angiogenic Signaling Triggered by Cariogenic Bacteria in Pulp Cells |
LTA, VEGF |
LTA induces VEGF upregulation in pulp cells via P13K-Akt signaling |
10 | 37 |
2012 |
Kraus et al. |
Interactions of Adiponectin and Lipopolysaccharide from Porphyromonas gingivalis |
LPS, IL-1β, IL-6, IL-8,IL-10 |
LPS significantly up-regulate IL-1β, IL-6, IL-8, IL-10 expressions. |
11 | 38 |
2012 |
Maciel et al. |
Cytokine expression in response to root canal infection in gnotobiotic mice |
Fusobacteriumnucleatum,peptostreptococcus prevotii IFN-g, TNF-a, IL-10, IL-4, TGF-b |
Different bacteria have different effect on cytokines levels. F. nucleatum causes increase in IFN-g, TNF-a, IL-4. IL-10 is induced by either one of the two bacteria. TGF-b is induced by combination of the two bacteria. |
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