MyD88 is essential for alveolar bone loss induced by<i>Aggregatibacter actinomycetemcomitans</i>LPS in mice

Madeira, M. F. M.; Queiroz-Júnior, Celso Martins; Cisalpino, Daniel; Werneck, Silvia Maria Cordeiro; Kikuchi, Hitoshi; Fujise, O.; Ryffel, Bernhard; Silva, T. A.; Teixeira, Mauro Martins; Souza, Danielle G.

doi:10.1111/j.2041-1014.2013.12034.x

Cited by 7 publications

(19 citation statements)

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“…Despite the surgical and nonsurgical therapeutic options, the global prevalence of PD is remarkably high (40%‐90%) . Activation of the toll‐like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) pathway in response to excessive stimulation of the host immune system against periodontopathogenic bacteria may underpin the pathophysiology of PD . Through the up‐regulation of nuclear factor‐kappa B (NF‐κB) and phosphorylation of the extracellular regulated protein kinase (ERK) transduction cascades, activation of the TLR4/MyD88 pathway could induce the synthesis and release of a variety of pro‐inflammatory cytokines [eg, interleukin 1β (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor α (TNF‐α)], consequently destroying the periodontal tissues .…”

Section: Introductionmentioning

confidence: 99%

Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway

Renn

Huang

Feng

et al. 2018

Journal of Pineal Research

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Periodontitis (PD) is an inflammatory disease characterized by gingival inflammation and resorption of alveolar bone. Impaired receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) signaling caused by enhanced production of pro-inflammatory cytokines plays an essential role in the pathogenesis of PD. Considering melatonin possesses significant anti-inflammatory property, this study aimed to determine whether prophylactic treatment with melatonin would effectively normalize RANKL/OPG signaling, depress toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88)-mediated pro-inflammatory cytokine activation, and successfully suppress the pathogenesis of PD. PD was induced in adult rats by placing the ligature at molar subgingival regions. Fourteen days before PD induction, 10, 50, or 100 mg/kg of melatonin was intraperitoneally injected for consecutive 28 days. Biochemical and enzyme-linked immunosorbent assay were used to detect TLR4/MyD88 activity, RANKL, OPG, interleukin 1β, interleukin 6, and tumor necrosis factor-α levels, respectively. The extent of bone loss, bone mineral intensity, and calcium intensity was further evaluated by scanning electron microscopy, micro-computed tomography, and energy-dispersive X-ray spectroscopy. Results indicated that high RANKL/OPG ratio, TLR4/MyD88 activity, and pro-inflammatory cytokine levels were detected following PD. Impaired biochemical findings paralleled well with severe bone loss and reduced calcium intensity. However, in rats pretreated with melatonin, all above parameters were successfully returned to nearly normal levels with maximal change observed in rats receiving 100 mg/kg. As prophylactic treatment with melatonin effectively normalizes RANKL/OPG signaling by depressing TLR4/MyD88-mediated pro-inflammatory cytokine production, dietary supplement with melatonin may serve as an advanced strategy to strengthen oral health to counteract PD-induced destructive damage.

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Section: Introductionmentioning

confidence: 99%

Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway

Renn

Huang

Feng

et al. 2018

Journal of Pineal Research

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“…Induction of osteoclastogenesis due to cleavage of osteoprotegerin [30,49] C. rectus LPS: Stimulation of synthesis by gingival prostaglandin fibroblasts е2, il-1 and il-6 [32] Groel: Induces secretion by gingival cells il-6 and il-8 [38,45] T. denticola Chymotrypsin-like protease: Lysis of the components of the intercellular matrix (hyaluronic acid, chondroitin sulfate, fibronectin, laminin, fibrinogen) [16,17] A. actinomycetocomitans 1. Activation TLR-4 and myd88: Stimulation of differentiation of blood monocytes into osteoclasts [22] 2. Stimulation of RANKL B-lymphocyte synthesis and activation of osteoclasts [50] T. forthisia o-glycans: Inhibition of t1 response [24] LPS: Induction of il-6 synthesis, tnfb by gingival fibroblasts BspA: Induction of the th2 response associated with bone resorption [25] 1.…”

Section: Discussionmentioning

confidence: 99%

“…LPS interacts with the toll-like receptor 4, which leads to activation of the MyD88 signal protein (the primary response protein of myeloid differentiation 88). [22] According to the data, in addition to innate immunity, the role of adaptive immune mechanisms also plays a role in the pathogenic action of A. actinomycetemcomitans.…”

Section: A Actinomycetemcomitansmentioning

confidence: 99%

Untitled

Batyrbekova¹

2017

AJP

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Pyoinflammatory diseases of maxillofacial area (MFA) are one of the most serious problems of maxillofacial surgery. The high medical and social significance of these diseases are due to their frequent occurrence in persons of working age and the risk of life-threatening complications: Bleeding from the great vessel, brain abscess, the spread of infection into the deep cellular spatium of the collum. In more than 1/3 of all patients, pyogenic lesions of MFA develop on the background of secondary immunodeficiency, accompanied by impaired regulation of the secretion of pro-inflammatory cytokines, and predisposing to prolonged smoldering flow or, on the contrary, rapid spread of inflammation with extensive tissue damage. This fact determines the importance of developing integrated approaches to diagnostics and treatment. The aim of the study is to generalize modern ideas about causative agents and their effect on the features of the inflammatory diseases of the MFA. We systematized and analyzed contemporary works of Russian and foreign authors on the study of the effects of causative agents of bacterial and viral nature and characteristic changes in the immune status. The modern data on the role of microbial factors in the development and maintenance of local and systemic immunological status disorders in case of inflammatory disease of MFA are presented, the impact on the development of bacterial and viral microflora diseases is given, with special attention paid to immunomodulatory effects of causative agents. The factors of pathogens influence most frequently associated with inflammatory diseases of theMFA and collum, as well as the relationship of individual microorganisms with the clinical manifestations of this pathology type and the detection of the pathogenetic role of immune disorders, allow to conduct studies on the formation of optimal correction schemes for each patient (personified) depending on the features of the course of the disease.

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“…The pathogen, the nonmotile Gram-negative facultative anaerobe Aggregatibacter actinomycetemcomitans (Aa), is a contributing agent of periodontitis (gum disease) (11), one of the most prevalent infectious diseases worldwide (12). Aa elaborates an array of virulence factors that enhance its survival and directly harm the host during infection, including leukotoxin (13), cytolethal distending toxin (14), CagE (15), fimbriae (16), and LPS (17). Several of these virulence factors contribute to bone loss, a signature of aggressive periodontitis, in various animal models (17,18).…”

mentioning

confidence: 99%

“…Aa elaborates an array of virulence factors that enhance its survival and directly harm the host during infection, including leukotoxin (13), cytolethal distending toxin (14), CagE (15), fimbriae (16), and LPS (17). Several of these virulence factors contribute to bone loss, a signature of aggressive periodontitis, in various animal models (17,18). However, despite Aa living in a microbe-rich environment, Aa-host interactions are less frequently investigated in the context of other oral microbes.…”

mentioning

confidence: 99%

Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection

Stacy

Everett

Jorth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

163

167

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The oral pathogen Aggregatibacter actinomycetemcomitans (Aa) resides in infection sites with many microbes, including commensal streptococci such as Streptococcus gordonii (Sg). During infection, Sg promotes the virulence of Aa by producing its preferred carbon source, L-lactate, a phenomenon referred to as cross-feeding. However, as with many streptococci, Sg also produces high levels of the antimicrobial hydrogen peroxide (H 2 O 2 ), leading to the question of how Aa deals with this potent antimicrobial during coinfection. Here, we show that Aa possesses two complementary responses to H 2 O 2 : a detoxification or fight response mediated by catalase (KatA) and a dispersion or flight response mediated by Dispersin B (DspB), an enzyme that dissolves Aa biofilms. Using a murine abscess infection model, we show that both of these responses are required for Sg to promote Aa virulence. Although the role of KatA is to detoxify H 2 O 2 during coinfection, 3D spatial analysis of mixed infections revealed that DspB is required for Aa to spatially organize itself at an optimal distance (>4 μm) from Sg, which we propose allows cross-feeding but reduces exposure to inhibitory levels of H 2 O 2 . In addition, these behaviors benefit not only Aa but also Sg, suggesting that fight and flight stimulate the fitness of the community. These results reveal that an antimicrobial produced by a human commensal bacterium enhances the virulence of a pathogenic bacterium by modulating its spatial location in the infection site.synergy | microbiota | microbial ecology | microenvironment | multispecies

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MyD88 is essential for alveolar bone loss induced byAggregatibacter actinomycetemcomitansLPS in mice

Cited by 7 publications

References 0 publications

Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway

Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway

Untitled

Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection

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