Influence of Periodontal Status and Periodontopathogens on Levels of Oral Human β‐Defensin‐2 in Saliva

Pereira, Alexandre Lustosa; Franco, Gilson César Nobre; Cortelli, Sheila Cavalca; Aquino, Davi Romeiro; Costa, Fernando Oliveira; Raslan, Suzane A; Cortelli, José Roberto

doi:10.1902/jop.2012.120321

Cited by 36 publications

(43 citation statements)

References 42 publications

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“…In periodontal disease, both HDP levels (43)(44)(45)(46)(47)(48) and the number of MRGPRX2-expressing mast cells are elevated (Fig. 2).…”

Section: Figmentioning

confidence: 96%

“…The findings of the current study provide the first demonstration that a significant increase in MRGPRX2-expressing mast cells is present in CP patients compared to the level in gingival tissue of healthy subjects. Considered in the context of studies reporting enhanced expression of hBDs and LL-37 in inflamed periodontal tissue relative to that in healthy tissue (43)(44)(45)(46)(47)(48), it is feasible that HDP-induced gingival mast cell degranulation via MRGPRX2 contributes to periodontal disease progression. In total, these findings imply that while low-level inflammation induced by /ml) and FAM-LL-37 (3 M) for 30 min, and degranulation was determined.…”

Section: Figmentioning

confidence: 99%

“…Indeed, antimicrobial HDPs released from the epithelium (human ␤-defensins [hBDs]) and from neutrophils (the cathelicidin LL-37) cause both mast cell chemotaxis and degranulation via the activation of MRGPRX2 (37)(38)(39)(40)(41)(42). It is noteworthy that expression of HDPs is upregulated in the gingiva and saliva of patients with periodontitis compared to that in the gingiva and saliva of healthy subjects (43)(44)(45)(46)(47)(48). These findings suggest that MRGPRX2-mediated activation of mast cells by HDPs contributes to host defense.…”

mentioning

confidence: 99%

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Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

et al. 2017

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Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690) to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation, but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449 may contribute to the modulation of disease progression.

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“…In periodontal disease, both HDP levels (43)(44)(45)(46)(47)(48) and the number of MRGPRX2-expressing mast cells are elevated (Fig. 2).…”

Section: Figmentioning

confidence: 96%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

et al. 2017

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“…Наруше-ния экспрессии дефенсинов выявлены при па-тологии различных отделов дыхательных путей и ротовой полости. Считается, что нарушение син-теза β-дефенсина hBD эпителием слизистой обо-лочки ротовой полости может быть причиной фор-мирования кандидоза полости рта и парадонтита [158]. Противоположное заключение было получе-но при исследовании концентрации β-дефенсина hBD-2 в ротовой полости у больных хроническим парадонтитом, ассоциированным с инфекцией Porphy romonas gingivalis [126].…”

Section: патогенетическое значение дефенCинов при инфекционных процессахunclassified

“…Установлено, что пептиды HD-2 активно продуци-руются клетками назального эпителия, в то время как фибробластами подслизистого слоя и клетка-ми назальных полипов данный β-дефенсин не про-дуцируется [56]. Данные одного из исследований показали, что воспаление периодонта сопровожда-лось снижением продукции β-дефенсинов HD-1, HD-2 и HD-3 [158]. Позже продемонстрировано, что протективный эффект слизистой ротовой полости в отношении Fusobacterium nucleatum и Prevotella intermedia реализуется при участии β-дефенсинов HD-1 и HD-3 [81].…”

Section: патогенетическое значение дефенCинов при инфекционных процессахunclassified

Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy

Vaschenko

Иванович²,

Vilyaninov

et al. 2016

Rev Clin Pharm Drug Ther

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Ключевые слова:антимикробные пептиды; дефенсины человека; механизм действия дефенсинов; вирусы; антивирусные препараты. РезюмеДефенсины человека -катионные антимикробные пептиды (АМП) нейтрофилов и клеток барьерных эпителиев -явля-ются одними из ключевых молекул врожденного иммунитета, обеспечивающих противоинфекционную защиту организма. Дефенсины обладают высокой антимикробной, противовирус-ной, липополисахарид-связывающей активностью, ряд дефен-синов проявляет цитотоксическую активность в отношении опухолевых и нормальных клеток человека in vitro, некоторые АМП оказывают ранозаживляющее действие. Кроме анти-микробного действия АМП проявляют также широкий спектр эффектов в отношении собственных клеток организма людей. Это дает основание рассматривать данные пептиды не только как антимикробные, но и как возможные биомодуляторные соединения. Отдельные представители семейства дефенси-нов обладают кортикостатической активностью: ингибируют стимулированный адренокортикотропным гормоном стеро-идогенез в клетках коркового слоя надпочечников in vitro, а также совместно с протегрином-3 снижают уровень кортико-стерона в крови животных, повышение которого индуцировано адренокортикотропным гормоном или стрессом. Описанные в литературе данные свидетельствуют в пользу концепции дефенсинов человека как многофункциональных молекул, участвующих во взаимодействии систем врожденного и приоб-ретенного иммунитета, а также иммунной и нейроэндокринной систем. Акцентируется внимание на патогенезе противовирус-ного действия и перспективах использования природных и син-тетических дефенсинов в терапии инфекционных заболеваний. ANTIMICROBIAL AND ANTIVIRAL EFFECTS OF HUMAN DEFENSINS Keywords: antimicrobial peptides; human defensins; mode of action; viruses; antiviral drugs. Abstract. Defensins, the cationic antimicrobial pep tides (AMPs) of phagocytes and epithelial cells, are the key effector molecules of the innate immune system providing the anti-infective host defense. Besides the antimicrobial action, AMPs exert a broad spectrum of varied effects towards host cells giving a ground for considering these peptides as possible biomodulatory molecules. The review outlines different types of the biological activity of structurally diverse AMPs. AMPs posses the potent antimicrobial, antiviruses and lipopolysaccharide-binding activity; some of them are cytotoxic for tumor and normal human cells in vitro, while others demonstrate the wound healing action. AMPs of the defensin family display the corticostatic activity: they inhibit stimulated by adrenocorticotropic hormone (ACTH) steroidogenesis in adrenal cells in vitro. We also showed that defensins and protegrin 3 abolish ACTH-or stressinduced increase of the corticosterone level in blood of experimental animals. Taken together, the described in the literature and our own data contribute to the idea that AMPs are the multifunctional molecules participating in the interaction between the innate and adaptive immune systems as well as between immune and neuroendocrine systems. It considers st...

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Serum, saliva, and gingival tissue human β‐defensin levels in relation to retinoic acid use

Atalay

Balcı

Toygar

et al. 2022

Journal of Periodontology

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Background: Retinoic acid is an active derivative of vitamin A and regulates the differentiation, proliferation, and antimicrobial peptide expression profiles of human cells. The aim of the present study was to analyze the effect of systemic retinoic acid use on serum, saliva, and gingival tissue levels of human β-defensin (hBD)-1, hBD-2, and hBD-3.Methods: A total of 69 participants (34 systemic retinoic acid users and 35 healthy controls) were enrolled in this study. Plaque index, probing pocket depth, bleeding on probing (BOP), and clinical attachment loss were measured. Saliva and serum hBD-1, hBD-2, and hBD-3 levels were quantified by enzyme-linked immunosorbent assay. Gingival tissue hBD-1, hBD-2, and hBD-3 levels were determined by immunohistochemistry. A univariate general linear model was used in adjusted comparisons of hBD1, hBD-2, and hBD-3. P values of < 0.05 were considered statistically significant. Results: Reduced salivary levels of hBD-2 (P = 0.042), but not hBD-1 or hBD-3, were detected in systemic retinoic acid users compared to non-user controls. There was a significant difference in the adjusted (for BOP%) salivary hBD-2 concentrations between retinoic acid and control groups (P = 0.031). No difference was observed in serum or tissue levels of hBD-1, hBD-2, or hBD-3 between the two study groups. Conclusion:Systemic retinoic acid use was associated with suppressed salivary hBD-2 level, which was independent of gingival inflammation.

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Influence of Periodontal Status and Periodontopathogens on Levels of Oral Human β‐Defensin‐2 in Saliva

Cited by 36 publications

References 42 publications

Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy

Serum, saliva, and gingival tissue human β‐defensin levels in relation to retinoic acid use

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