Signaling Pathways Activation by Primary Endodontic Infectious Contents and Production of Inflammatory Mediators

Martinho, Frederico Canato; Leite, Fábio Renato Manzolli; Chiesa, Wanderson Miguel Maia; Nascimento, Gustavo G.; Feres, Magda; Gomes, Brenda Paula Figueiredo de Almeida

doi:10.1016/j.joen.2013.10.022

Cited by 32 publications

(25 citation statements)

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“…Gramnegative and -positive bacteria, including Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Pseudomonas aeruginosa, Bacteroides forsythus, Campylobacter rectus, Peptostreptococcus micros, Staphylococcus intermedius, and Treponema sp. play an important role in the pathophysiology of periodontitis and CAP [22,32,33]. There are, however, no data whether LPS levels in the root canals of patients with CAP are associated with depression and systemic O&NS processes.…”

Section: Introductionmentioning

confidence: 99%

Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life

et al. 2017

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Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways. This present study examined the associations among chronic apical periodontitis (CAP), root canal endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms, and quality of life. Measurements included advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), -sulfhydryl (SH) groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase (PON)1 activity in participants with CAP, with and without depression, as well as healthy controls (no depression, no CAP). Root canal LPS levels were positively associated with CAP, clinical depression, severity of depression (as measured with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP participants, there was a strong correlation (r = 0.734, p < 0.001) between root canal LPS and the HDRS score. There were significant and positive associations between CAP or root canal endotoxin with the vegetative and physio-somatic symptoms of the HDRS as well as a significant inverse association between root canal endotoxin and quality of life with strong effects on psychological, environmental, and social domains. It is concluded that increased root canal LPS accompanying CAP may cause depression and a lowered quality of life, which may be partly explained by activated O&NS pathways, especially NOx thereby enhancing hypernitrosylation and thus neuroprogressive processes. Dental health and "leaky teeth" may be intimately linked to the etiology and course of depression, while significantly impacting quality of life.

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Section: Introductionmentioning

confidence: 99%

Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life

et al. 2017

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“…Additionally, P. endodontalis LPS increased expression of TRIB3 in osteoblasts after 10 h simulated time. Overexpression of TRIB3 enhanced NF-jB phosphorylation and Wnt5a induction, whereas knockdown of TRIB3 inhibited NF-jB phosphorylation and Wnt5a expression in P. endodontalis LPS-stimulated INTRODUCTION Gram-negative anaerobic microorganisms play crucial roles in endodontal and periodontal infections, and among them, Porphyromonas endodontalis is the most commonly implicated in the etiology of infected root canals and apical lesions (Tomazinho & Avila-Campos, 2007;Montagner et al, 2012;Martinho et al, 2014). A major virulence factor of P. endodontalis is lipopolysaccharide (LPS), which plays critical roles in inducing the secretion of proinflammatory cytokines and in bone destruction (Yang et al, 2009;Tang et al, 2011;Guo et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Porphyromonas endodontalis is considered to be an important member of the Gram-negative anaerobic microorganisms involved in infected root canals and apical periodontitis (Tomazinho & Avila-Campos, 2007;Montagner et al, 2012;Martinho et al, 2014). The major constituent of its outer membrane, LPS, has been proved to play a critical role in initiating and developing periapical periodontitis and the odontogenic abscess by mediating inflammation and inducing cells to secrete proinflammatory cytokines (Murakami et al, 2001;Yang et al, 2009;, 2011; Guo et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Gram‐negative anaerobic microorganisms play crucial roles in endodontal and periodontal infections, and among them, Porphyromonas endodontalis is the most commonly implicated in the etiology of infected root canals and apical lesions (Tomazinho & Avila‐ Campos, ; Montagner et al ., ; Martinho et al ., ). A major virulence factor of P. endodontalis is lipopolysaccharide (LPS), which plays critical roles in inducing the secretion of proinflammatory cytokines and in bone destruction (Yang et al ., ; Tang et al ., ; Guo et al ., ).…”

Section: Introductionmentioning

confidence: 97%

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TRIB3 mediates the expression of Wnt5a and activation of nuclear factor‐κB in Porphyromonas endodontalis lipopolysaccharide‐treated osteoblasts

Qiu

Guo

et al. 2015

Molecular Oral Microbiology

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Porphyromonas endodontalis lipopolysaccharide (LPS) is considered to be correlated with the progression of bone resorption in periodontal and periapical diseases. Wnt5a has recently been implicated in inflammatory processes, but its role is unclear as a P. endodontalis LPS-induced mediator in osteoblasts. Tribbles homolog 3 (TRIB3) encodes a pseudokinase and has been linked to inflammation in certain situations. Here, we found that P. endodontalis LPS induced Wnt5a expression in a dose- and time-dependent manner and it also upregulated translocation, phosphorylation and transcriptional activity of nuclear factor-κB (NF-κB) in MC3T3-E1 cells. Bay 11-7082 blocked the translocation of NF-κB and Wnt5a expression induced by P. endodontalis LPS. Chromatin immunoprecipitation assay further established that induction of Wnt5a by P. endodontalis LPS was mediated through the NF-κB p65 subunit. Additionally, P. endodontalis LPS increased expression of TRIB3 in osteoblasts after 10 h simulated time. Overexpression of TRIB3 enhanced NF-κB phosphorylation and Wnt5a induction, whereas knockdown of TRIB3 inhibited NF-κB phosphorylation and Wnt5a expression in P. endodontalis LPS-stimulated osteoblasts. These results suggest that P. endodontalis LPS has the ability to promote the expression of Wnt5a in mouse osteoblasts, and this induction is mainly mediated by NF-κB pathway. TRIB3 seems to modulate the sustained expression of Wnt5a in osteoblasts stimulated by P. endodontalis LPS, as well as regulating NF-κB phosphorylation.

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“…Propiobacterium acnes (red complex) [23,24]. Similar problems can be caused by chronic jaw cavitations or inflammations around implants, which continuously produce pro-inflammatory factors/ cytokines, like TNF alpha, IL1beta, IL2 and IL6 or the chemokine RANTES [25][26][27][28][29][30].…”

Section: The Uro-nephological System and Important Cam Relationshipsmentioning

confidence: 99%

Basics and Examples of Successful Treatment of Uro-nephrological Diseases (In The Context of CAM)

Oettmeier¹,

Vizkelety²

2017

J Med - Clin Res & Rev

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In regards to conventional diagnostic and treatment modalities of uronephrological diseases, complementary and alternative medicine (CAM) applies evidence-based aspects of environmental medicine (toxins, physical irritating fields), of vegetative nervous system (reflex zones, sympatheticparasympathetic balance, somatotopies, odontomas), of energetic medicine (acupuncture meridians of TCM, chakras from Ayurvedic medicine) as well as approved psycho-mentally and psycho-emotionally aspects. The uronephrological system is embedded in this holistic context, which enables a clear diagnostic strategy to develop an individual therapeutic concept. With these applications, it is possible to treat more preciously the complex reasons of the disease. As a primary measure, it is necessary to reduce the environmental toxic load, to optimize the dental situation (removal of dental foci) and to diminish chronic neuro-modulative triggers (foci) with the help of neural therapy. As a secondary measure we pay attention to the intestinal health and immune system. Last but not least, the patient's own healing forces need to be activated by using a vast spectrum of natural remedies and organ cell therapy. The examples of chronic cystitis, nephrotic syndrome and membrane-proliferative glomerulonephritis illustrate the successful application of CAM in this fields.

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Signaling Pathways Activation by Primary Endodontic Infectious Contents and Production of Inflammatory Mediators

Cited by 32 publications

References 31 publications

Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life

Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life

TRIB3 mediates the expression of Wnt5a and activation of nuclear factor‐κB in Porphyromonas endodontalis lipopolysaccharide‐treated osteoblasts

Basics and Examples of Successful Treatment of Uro-nephrological Diseases (In The Context of CAM)

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