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Microbial Pathogenesis Mar 2022Endotoxin tolerance refers to a state refractory to subsequent lipopolysaccharide (LPS) stimulations following a primary LPS exposure. To study the relationship between...
Endotoxin tolerance refers to a state refractory to subsequent lipopolysaccharide (LPS) stimulations following a primary LPS exposure. To study the relationship between endotoxin tolerance and macrophage polarization, endotoxin tolerance was induced by 1 μg/mL LPS from the periodontal pathogen, Porphyromonas gingivalis (P. gingivalis), in peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs). Repeated P. gingivalis LPS challenges increased the quantities of CD206+ PMs, while the number of CD86+CD206+ PMs was reduced compared with the non-tolerant group (p < 0.05). However, there were no changes in BMDMs (p > 0.05). Down regulations of TNF-α, IL-12, nitric oxide and MMP-2 production, and upregulated IL-10, MMP-9 levels and arginase-1 activities occurred in tolerant PMs and BMDMs (p < 0.05). P. gingivalis LPS-tolerant PMs and BMDMs also enhanced scrape-wound healing abilities of 15p-1 cells (p < 0.05). Expressions of phospho-signal transducer and activator of transcription 6 (p-STAT6) and protein tyrosine phosphatase 1B (PTP1B) were increased, while p-MEK1/2 levels were downregulated in tolerant PMs and BMDMs (p < 0.05). IL-10 production in tolerant Stat6 knockdown RAW264.7 cells was lower than tolerant control cells (p < 0.05). P. gingivalis LPS-tolerant macrophages represented an intermediate state between M1/M2 polarization, which functioned as M2-like cells, and led to limited inflammatory responses and enhanced wound healing activities. The PTP1B-MEK1/2-STAT6 signaling pathway might be involved in the polarization of tolerant macrophages.
Topics: Endotoxin Tolerance; Lipopolysaccharides; Macrophage Activation; Macrophages; Porphyromonas gingivalis
PubMed: 35189277
DOI: 10.1016/j.micpath.2022.105448 -
Research in Microbiology 2022The phosphopantetheinyl transferases (PPTases) catalyze the post-translational modification of carrier proteins (CPs) from fatty acid synthases (FASs) in primary...
The phosphopantetheinyl transferases (PPTases) catalyze the post-translational modification of carrier proteins (CPs) from fatty acid synthases (FASs) in primary metabolism and from polyketide synthases (PKSs) and non-ribosomal polypeptide synthases (NRPSs) in secondary metabolism. Based on the conserved sequence motifs and substrate specificities, two types (AcpS-type and Sfp-type) of PPTases have been identified in prokaryotes. We present here that Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, harbors merely one PPTase, namely PptP. Complementation and gene deletion experiments clearly show that PptP can replace the function of Escherichia coli AcpS and is essential for the growth of P. gingivalis. Purified PptP transfers the 4-phosphopantetheine moiety of CoA to inactive apo-acyl carrier protein (ACP) to form holo-ACP, which functions as an active carrier of the acyl intermediates of fatty acid synthesis. Moreover, PptP exhibits broad substrate specificity, modifying all ACP substrates tested and catalyzing the transfer of coenzyme A (CoA) derivatives. The lack of sequence alignment with known PPTases together with phylogenetic analyses revealed PptP as a new class of PPTases. Identification of the new PPTase gene pptP exclusive in Porphyromonas species reveals a potential target for treating P. gingivalis infections.
Topics: Acyl Carrier Protein; Bacterial Proteins; Coenzyme A; Escherichia coli; Phylogeny; Porphyromonas; Transferases (Other Substituted Phosphate Groups)
PubMed: 35337986
DOI: 10.1016/j.resmic.2022.103940 -
Deciphering the toxicological role of Porphyromonas gingivalis derived endotoxins in liver diseases.Environmental Toxicology and... Nov 2021Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues.... (Review)
Review
Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues. Porphyromonas gingivalis, a Gram‑negative oral anaerobe, mainly causes periodontitis and it is one of the most important risk factors responsible for aggravation of existing systemic diseases. Several experimental and clinical studies have shown the positive association between periodontitis and different forms of liver disease. Periodontal diseases increase the prevalence of non-alcoholic fatty liver diseases and cirrhosis. Infected periodontium and pathogens in the periodontal microenvironments release pathogen-associated molecular patterns such as peptidoglycan, lipopolysaccharides, gingipain, fimbria, bacterial DNA, etc, and damage-associated molecular patterns such as interleukins-1α, β, - 8, and galectin-3, etc. These virulence factors and cytokines enter the bloodstream, disseminate into the whole body, and induce a variety of systemic pathological effects, including liver diseases (steatosis and fibrosis). Maintaining oral hygiene by scaling and root planning significantly improves liver damage in patients with periodontitis. Dentists and physicians should have more awareness in understanding the bidirectional nature of the relationship between oral and systemic diseases. Importantly, periodontitis condition aggravates simple fatty liver into fibrotic disease and therefore, the aim of this review is to understand the possible link between periodontitis and liver diseases.
Topics: Animals; Bacteroidaceae Infections; Endotoxins; Humans; Life Style; Liver Diseases; Oral Hygiene; Periodontitis; Porphyromonas gingivalis
PubMed: 34662732
DOI: 10.1016/j.etap.2021.103755 -
Canadian Journal of Dental Hygiene :... Feb 2023Research has suggested 2 potential mechanisms by which the periodontal inflammatory response may communicate to distant organs: 1) direct translocation of periodontal... (Review)
Review
BACKGROUND
Research has suggested 2 potential mechanisms by which the periodontal inflammatory response may communicate to distant organs: 1) direct translocation of periodontal bacteria from the oral cavity to another organ system; and 2) inflammation as a result of metastatic periodontal inflammation. The purpose of this scoping review is to explore these mechanisms as potential mediators between periodontitis and Alzheimer's disease.
METHODS
A reiterative literature search of peer-reviewed articles was performed in the PubMed and Scopus databases using keywords or combinations such as Alzheimer's disease AND periodontitis OR periodontal disease AND inflammation.
RESULTS
A total of 777 articles were identified. After eliminating duplicates and reviewing titles and abstracts, 84 articles were selected for full-text review. Following full-text review, 19 articles met the eligibility criteria for the study.
DISCUSSION
The review of the literature highlights how periodontitis may contribute to neuroinflammation by the introduction of periodontal bacteria and/or proinflammatory cytokines locally produced at the periodontium.
CONCLUSION
Inflammation is an important mechanism in the onset and progression of both periodontitis and Alzheimer's disease. Nevertheless, further studies are necessary to better understand the multifactorial pathogenesis of Alzheimer's disease.
Topics: Humans; Porphyromonas gingivalis; Alzheimer Disease; Periodontitis; Periodontium; Inflammation
PubMed: 36968797
DOI: No ID Found -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2021Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them. (Review)
Review
BACKGROUND
Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them.
MATERIAL AND METHODS
Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed.
RESULTS
A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases.
CONCLUSIONS
Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association.
Topics: Head and Neck Neoplasms; Humans; Periodontitis; Porphyromonas gingivalis; Risk Factors
PubMed: 33340075
DOI: 10.4317/medoral.24270 -
A Boolean Network Approach to Study the Mechanism Associated with Inflammatory Response Induced by .Archives of Razi Institute Feb 2023Anaerobic is a rod-shaped bacterium and is a primary agent of periodontal inflammation and thus periodontitis. This bacterium disturbs the normal flora of the oral... (Review)
Review
Anaerobic is a rod-shaped bacterium and is a primary agent of periodontal inflammation and thus periodontitis. This bacterium disturbs the normal flora of the oral cavity and causes dysbiosis. Databases including Google Scholar Scopus and PubMed were employed to find the evidence by using keywords like ',' 'Boolean network,' 'inflammatory response and ,' 'inflammation and . Only articles that reviewed the role of in oral inflammation were selected. promotes and reorganizes host immune systems against normal host flora, which causes a dysbiotic state. A reorganized immune system induces dysbiosis and periodontitis. Specifically, the role of the C5a receptor in the complement system is vital in this mechanism. can change the metabolic pathways of phagocytic cells without impeding inflammation. Toll-like receptor and complement signaling are inverted by , which aids them in overcoming immunological responses. However, they sustain the inflammation process, which promotes dysbiosis. Instead of a subjective approach, a systems perspective is required to comprehend this intricate process. A Boolean network is a system approach that seems to be a better approach to understanding this complicated interaction process of with the immune system and inflammation. In short, attempts to understand the complex process using the Boolean network will ultimately help in the early detection of periodontitis, and immediate treatment can prevent soft tissue destruction and dentition loss.
Topics: Animals; Dysbiosis; Porphyromonas gingivalis; Inflammation; Hydrolases
PubMed: 37312726
DOI: 10.22092/ARI.2021.356604.1877 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2022Periodontitis, one of the most common inflammatory oral diseases in human beings, threatens the health of teeth and mouth and is closely associated with the development... (Review)
Review
Periodontitis, one of the most common inflammatory oral diseases in human beings, threatens the health of teeth and mouth and is closely associated with the development of many systemic diseases. Existing research about the pathogenesis of periodontitis mainly focuses on the oral microbial homeostasis and its complex interaction with the immune system. Among all the oral microorganisms, ( ) is considered to be the main pathogen causing chronic periodontitis. Recent studies have shown that poesseses HmuY, a special heme binding protein, which binds with heme to provide essential nutrition for and activates the host immune system. Therefore, HmuY plays an important role in the growth, proliferation, invasion, and pathogenesis of and is a potential virulence factor of the bacteria. Existing studies on HmuY are limited to the host immune response that HmuY triggers, and there are still no conclusive findings on whether HmuY participates in the pathogenesis of periodontitis through other ways, such as influencing periodontal bone metabolism. Herein, we reviewed the latest research findings on the biological characteristics and physiological functions of HmuY and its relationship with chronic periodontitis, so as to provide new ideas for in-depth research and further explorations into the pathogenesis of chronic periodontitis.
Topics: Humans; Porphyromonas gingivalis; Chronic Periodontitis; Face; Nutritional Status
PubMed: 36443060
DOI: 10.12182/20221160208 -
Journal of Dental Research Apr 2021Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely... (Review)
Review
Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as , through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostatic metabolic pathways for successful bacterial persistence. As the overgrowth of colonizing microorganisms in the gingival mucosa can shift from homeostasis to dysbiosis or a diseased state, it is crucial to understand how the innate modulatory molecules are intricately involved in antibacterial pathways and how they shape susceptibility versus resistance in the epithelium toward pathogens. Thus, in this review, we highlight recent discoveries in gingival epithelial cell research in the context of bacterial colonizers. The current knowledge outlined here demonstrates the ability of epithelial cells to possess highly organized defense machineries, which can jointly regulate host-derived danger molecule signaling and integrate specific global responses against opportunistic bacteria to combat microbial incursion and maintain host homeostatic balance. These novel examples collectively suggest that the oral epithelia are equipped with a dynamically robust and interconnected defense system encompassing sensors and various effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria.
Topics: Epithelial Cells; Gingiva; Homeostasis; Mouth Mucosa; Porphyromonas gingivalis
PubMed: 33203318
DOI: 10.1177/0022034520973012 -
Annals of Surgical Oncology Dec 2023The association between oral microbiota and pancreatic cancer (PC) is increasingly recognized and studied. Yet, contrasting results are seen in current studies. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between oral microbiota and pancreatic cancer (PC) is increasingly recognized and studied. Yet, contrasting results are seen in current studies. This study aimed to provide systematic review and meta-analysis comparing PC and oral microbiota.
METHODS
Studies related to the association between oral microbiota and PC were identified through digital databases including PubMed, Medline, EMBASE, COCHRANE, and SCOPUS without limitations on language or publication period. The last identification date was 10 March 2023. Three case-control studies concerning the issue were included. For the meta-analyses, RevMan software version 5.4 was used. The Newcastle-Ottawa scale was used to evaluate articles and measurement of study differences, and publication bias was shown.
RESULTS
Porphyromonas gingivalis in oral bacteria was detected at a comparatively high detection rate in PC patients compared with healthy controls (odds ratio [OR], 1.38; 95 % confidence interval [CI], 1.09-1.74; P = 0.007; I = 34 %). The detection rate did not differ significantly between PC patients and healthy control patients for Aggregatibacter actinomycetemcomitans (OR 0.98; 95 % CI 0.75-1.29; P = 0.90; I = 76 %); Tannerella forsythiaand (OR 1.12; 95 % CI 0.89-1.42; P = 0.33; I = 0 %), or Prevotella intermedia (OR 1.08; 95 % CI 0.84-1.39; P = 0.55; I = 0 %).
CONCLUSION
Oral microbiota were closely related to PC, whereas P. gingivalis was more commonly found in the PC patients than in the healthy controls. For patients with PC, P. gingivalis may play a role in early diagnosis.
Topics: Humans; Porphyromonas gingivalis; Prevotella intermedia; Pancreatic Neoplasms; Microbiota
PubMed: 37787951
DOI: 10.1245/s10434-023-14366-7 -
Stem Cells and Development Dec 2021Mesenchymal stem cells (MSCs) are increasingly used in tissue regeneration, not only because of their multilineage differentiation ability, but also because of their... (Review)
Review
Mesenchymal stem cells (MSCs) are increasingly used in tissue regeneration, not only because of their multilineage differentiation ability, but also because of their immunomodulatory function, which allows them to play a role in the inflammatory milieu, especially in periodontitis. () is an important pathogen associated with the progression of periodontitis. Heterogeneous MSC sources show differences in their inflammatory-immune responsiveness and osteogenesis capabilities when exposed to and its virulence factors. This article reviews the promoted inflammatory and immune responses of periodontal ligament stem cells, which are potential pitfalls in bone regeneration. MSCs from other sources showed contradictory inflammatory and immune reactions in the few studies on this topic. We also summarize the mechanisms involved in the inflammatory, immune responses and osteogenic potential of MSCs exposed to and its virulence factors to inform an improved utilization of MSCs in regenerative therapies for periodontitis.
Topics: Cells, Cultured; Immunity; Mesenchymal Stem Cells; Osteogenesis; Periodontal Ligament; Porphyromonas gingivalis
PubMed: 34628938
DOI: 10.1089/scd.2021.0068