Understanding the role of endotoxin tolerance in chronic inflammatory conditions and periodontal disease

2021 ◽  
Author(s):  
Lena Larsson ◽  
Carlos Garaicoa‐Pazmino ◽  
Farah Asa'ad ◽  
Rogerio M. Castilho
Keyword(s):  
Periodontal Disease ◽  
Endotoxin Tolerance ◽  
Inflammatory Conditions

scholarly journals Elevated Expression of Cathepsin K in Periodontal Ligament Fibroblast by Inflammatory Cytokines Accelerates Osteoclastogenesis via Paracrine Mechanism in Periodontal Disease

2021 ◽  
Vol 22 (2) ◽  
pp. 695
Author(s):  
Soon Chul Heo ◽  
Yu Na Kim ◽  
YunJeong Choi ◽  
Ji-Young Joo ◽  
Jae Joon Hwang ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Cytokines ◽  
Periodontal Ligament ◽  
Cathepsin K ◽  
Periodontal Ligament Fibroblasts ◽  
Supporting Cells ◽  
Inflammatory Conditions ◽  
Elevated Expression ◽  
Macrophage Colony

Cathepsin K (CTSK) is a cysteine protease that is mainly produced from mature osteoclasts and contributes to the destruction of connective tissues and mineralized matrix as a consequence of periodontal disease (PD). However, few studies have reported its regulatory role in osteoclastogenesis-supporting cells in inflammatory conditions. Here, we investigated the role of CTSK in osteoclastogenesis-supporting cells, focusing on the modulation of paracrine function. Microarray data showed that CTSK was upregulated in PD patients compared with healthy individuals, which was further supported by immunohistochemistry and qPCR analyses performed with human gingival tissues. The expression of CTSK in the osteoclastogenesis-supporting cells, including dental pulp stem cells, gingival fibroblasts, and periodontal ligament fibroblasts (PDLFs) was significantly elevated by treatment with inflammatory cytokines such as TNFα and IL-1β. Moreover, TNFα stimulation potentiated the PDLF-mediated osteoclastogenesis of bone marrow-derived macrophages. Interestingly, small interfering RNA-mediated silencing of CTSK in PDLF noticeably attenuated the TNFα-triggered upregulation of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, and RANKL/osteoprotegerin ratio, thereby abrogating the enhanced osteoclastogenesis-supporting activity of PDLF. Collectively, these results suggest a novel role of CTSK in the paracrine function of osteoclastogenesis-supporting cells in periodontal disease.

scholarly journals Role of Autoimmune Responses in Periodontal Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Soumya Nair ◽  
Mohamed Faizuddin ◽  
Jayanthi Dharmapalan
Keyword(s):  
Periodontal Disease ◽  
Dental Plaque ◽  
Tooth Loss ◽  
Genetic Factors ◽  
Periodontal Diseases ◽  
Inflammatory Conditions ◽  
Shock Proteins ◽  
Supporting Structures ◽  
Induce Antibody

Periodontal diseases are characterized by localized infections and inflammatory conditions that directly affect teeth supporting structures which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidences of involvement of immunopathology have been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. This review is an attempt to throw light on the etiopathogenesis of periodontal disease highlighting the autoimmunity aspect of the etiopathogenesis involved in the initiation and progression of the disease. However, further clinical trials are required to strengthen the role of autoimmunity as a cause of periodontal disease.

scholarly journals Tobacco Use and Periodontal Disease—The Role of Microvascular Dysfunction

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 441
Author(s):  
Henrique Silva
Keyword(s):  
Periodontal Disease ◽  
Tobacco Use ◽  
Morphological Changes ◽  
Microvascular Dysfunction ◽  
Tobacco Exposure ◽  
Capillary Recruitment ◽  
Inflammatory Conditions ◽  
Nicotine Administration

Periodontal disease consists in highly prevalent wide-ranging inflammatory conditions that affect the supporting apparatus of teeth. Tobacco use is the most important risk factor for periodontal disease as it increases disease severity and periodontal surgery complications. Tobacco use is harmful for the vasculature by causing microvascular dysfunction, which is known to negatively affect periodontal disease. To the author’s knowledge this paper is the first comprehensive review on the mechanisms by which tobacco use affects oral microcirculation and impacts the pathophysiology of periodontal disease. In healthy subjects, acute nicotine administration or tobacco use (smoking/smokeless forms) increases the blood flow in the oral mucosa due to local irritation and increased blood pressure, which overcome neural- and endocrine-mediated vasoconstriction. Chronic tobacco smokers display an increased gingival microvascular density, which is attributed to an increased capillary recruitment, however, these microcirculatory units show higher tortuosity and lower caliber. These morphological changes, together with the repetitive vasoconstrictive insults, contribute to lower gingival perfusion in chronic smokers and do not completely regress upon smoking cessation. In periodontal disease there is considerable gingival inflammation and angiogenesis in non-smokers which, in chronic smokers, are considerably suppressed, in part due to local immune suppression and oxidative stress. Tobacco exposure, irrespective of the form of use, causes long-term microvascular dysfunction that increases the risk of complications due to the natural disease course or secondary therapeutic strategies.

Hyperferritinaemia: An Iron Sword of Autoimmunity

2019 ◽  
Vol 25 (27) ◽  
pp. 2909-2918 ◽  
Author(s):  
Joanna Giemza-Stokłosa ◽  
Md. Asiful Islam ◽  
Przemysław J. Kotyla
Keyword(s):  
Immune Response ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Catastrophic Antiphospholipid Syndrome ◽  
Inflammatory Conditions ◽  
Phase Reactant ◽  
Signalling Molecule ◽  
Cytokine Synthesis

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

scholarly journals Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 675
Author(s):  
Samira Elmanfi ◽  
Mustafa Yilmaz ◽  
Wilson W. S. Ong ◽  
Kofi S. Yeboah ◽  
Herman O. Sintim ◽  
...  
Keyword(s):  
Immune Response ◽  
Periodontal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Vaccine Adjuvants ◽  
Cyclic Dinucleotides ◽  
Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

The role of systemic conditions and disorders in periodontal disease

1993 ◽  
Vol 2 (1) ◽  
pp. 98-116 ◽  
Author(s):  
ROBERT J. GENCO ◽  
HARALD LÖE
Keyword(s):  
Periodontal Disease

Regulated proteolysis of p62/SQSTM1 enables differential control of autophagy and nutrient sensing

2018 ◽  
Vol 11 (559) ◽  
pp. eaat6903 ◽  
Author(s):  
Julia Sanchez-Garrido ◽  
Vanessa Sancho-Shimizu ◽  
Avinash R. Shenoy
Keyword(s):  
Nutrient Sensing ◽  
Caspase 8 ◽  
Rimmed Vacuoles ◽  
Sequestosome 1 ◽  
Inflammatory Conditions ◽  
Mtorc1 Signaling ◽  
Differential Control ◽  
Antimicrobial Immunity ◽  
Lateral Sclerosis

The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in SQSTM1, which encodes p62, are linked to hereditary inflammatory conditions such as Paget’s disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62TRM. We found that p62TRM, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic target of rapamycin complex 1 (mTORC1). The kinase RIPK1 and caspase-8 controlled p62TRM production and thus promoted mTORC1 signaling. An FTD-linked p62 D329G polymorphism and a rare D329H variant could not be proteolyzed by caspase-8, and these noncleavable variants failed to activate mTORC1, thereby revealing the detrimental effect of these mutations. These findings on the role of p62TRM provide new insights into SQSTM1-linked diseases and mTORC1 signaling.

scholarly journals Erythroplasia of Queyrat Treated with 5% Imiquimod Cream — Case Report Emphasizing the Role of Human Papilloma Virus Testing in a Clinical Setting

2017 ◽  
Vol 2 (1) ◽  
pp. 83-85
Author(s):  
Anca Chiriac ◽  
Piotr Brzezinski ◽  
Cristian Podoleanu ◽  
Simona Stolnicu
Keyword(s):  
Punch Biopsy ◽  
Imiquimod Cream ◽  
Once Daily ◽  
Public Health Burden ◽  
Inflammatory Conditions ◽  
Papillomavirus Infection ◽  
Compliant Patient ◽  
Erythroplasia Of Queyrat ◽  
Erythematous Plaques

AbstractBackground:Anogenital premalignancies and malignancies often affect females and males, and human papillomavirus infection plays a crucial role in their etiopathogenesis. These lesions are very important and represent an immense public health burden.Case presentation:A 78-year-old Caucasian male presented to the Dermatology Unit for persistent, slowly progressing, well-demarcated, erythematous plaques on the glans penis, observed by the patient 18 months prior to the consultation. Variable topical treatments were applied, with no improvement and with the denial of a punch biopsy. A clinical diagnosis of erythroplasia of Queyrat was established and the test for HPV revealed an association with subtype 16 (which excluded other benign inflammatory conditions). Positive results were obtained after 4 weeks of topical application of 5% imiquimod cream, once daily, 5 times a week.Conclusion:Erythroplasia of Queyrat should be diagnosed in a non-compliant patient based on the clinical picture and HPV testing even in the absence of a biopsy, and a non-surgical treatment should be initiated immediately.

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