&lt;p&gt;Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway&lt;/p&gt;

Huang, Cancan; Zhang, Chaotao; Yang, Panpan; Chao, Rui; Yue, Ziqi; Li, Congshan; Guo, Jie; Li, Minqi

doi:10.2147/dddt.s269223

Cited by 59 publications

(44 citation statements)

References 45 publications

(52 reference statements)

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“…On the other hand, O 3 did not affect surface protrusions in LPS-activated fibroblasts, whose control samples showed similar amounts of these membrane processes as the O 3 -treated non-activated fibroblasts. This is consistent with the finding that cultured fibroblasts treated with LPS increase their ROS production [35][36][37], which in turn affects the organization of cytoskeletal proteins [29][30][31]. It can therefore be inferred that the low O 3 concentrations tested in the present study are able to induce activation-like changes of the cell membrane in non-activated fibroblasts but do not affect already LPS-activated fibroblasts, thus avoiding their overstimulation and the possible scarring of the extracellular matrix [28].…”

Section: Discussionsupporting

confidence: 92%

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Cisterna

Costanzo

Lacavalla

et al. 2021

IJMS

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Oxygen–ozone (O2–O3) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O3 concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O2–O3 gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O3 stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-β1 secretion, while in LPS-activated fibroblasts, O3 stimulated only antioxidant response and cytokines secretion. Therefore, the low O3 concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated.

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Section: Discussionsupporting

confidence: 92%

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Cisterna

Costanzo

Lacavalla

et al. 2021

IJMS

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“…The NLRP3 inflammasome plays a crucial role in the pathogenesis and development of periodontal disease [ 4–7 ]. The suppression of the NLRP3 inflammasome enables alleviation of periodontitis in a mouse model [ 8 ]; meanwhile, NLRP3 knockout reduces periodontal bone loss during P. gingivalis infection in mice [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Microtubule affinity regulating kinase 4 promoted activation of the NLRP3 inflammasome-mediated pyroptosis in periodontitis

Wang

et al. 2021

Journal of Oral Microbiology

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Background Microtubule dynamics plays a crucial role in the spatial arrangement of cell organelles and activation of the NLRP3 inflammasome. Purpose This study aimed to explore whether microtubule affinity regulating kinase 4 (MARK4) can be a therapeutic target of periodontitis by affecting microtubule dynamics and NLRP3 inflammasome-mediated pyroptosis in macrophages. Materials and Methods The NLRP3 inflammasome-related genes and MARK4 were measured in the healthy and inflamed human gingival tissues. Bone marrow-derived macrophages (BMDMs) were infected with Porphyromonas gingivalis, while the MARK4 inhibitors (OTSSP167 and Compound 50) and small interference RNA were utilized to restrain MARK4. Apoptosis-associated speck-like protein (ASC) speck was detected by confocal, and levels of interleukin-1β (IL-1β), as well as IL-18, were assessed by ELISA. Results Increased staining and transcription of MARK4, NLRP3, ASC, and Caspase-1 were observed in the inflamed gingiva. P. gingivalis infection promoted MARK4 expression and the NLRP3 inflammasome in BMDMs. Inhibition of MARK4 decreased LDH release, IL-1β and IL-18 production, ASC speck formation, and the pyroptosis-related genes transcription. Furthermore, MARK4 inhibition reduced microtubule polymerization and acetylation in P. gingivalis- infected BMDMs. Conclusions MARK4 promoted NLRP3 inflammasome activation and pyroptosis in P. gingivalis- infected BMDMs by affecting microtubule dynamics. MARK4 inhibition might be a potential target in regulating the NLRP3 inflammasome during periodontitis progress.

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“…Oxidative stress induces pyroptosis of osteoblast-like MG63 cells by activating the NLRP3 inflammasome, thereby attenuating bone formation and promoting periodontitis; in contrast, an NLRP3 inhibitor reverses the reduction in osteoblast migration and COL1, RUNX2, and ALP levels ( 149 ). P. gingivalis activates the double-stranded RNA (dsRNA)-dependent kinase in osteoblastic MC3T3-E1 cells, thereby promoting NLRP3 expression by activating NF-κB, and LPS from P. gingivalis triggers NLRP3 inflammasome-dependent pyroptosis of gingival fibroblasts, which can be alleviated by eldecalcitol (a vitamin D analog) and inhibitors of ROS or NLRP3 ( 256 , 257 ). P. gingivalis and its LPS may also induce pyroptosis of gingival fibroblasts by activating NLRP6 and NLRP3 ( 176 , 182 ).…”

Section: Inflammasomes In Inflammatory Osteolysis Of the Alveolar Bone And Jawsmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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<p>Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway</p>

Cited by 59 publications

References 45 publications

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Microtubule affinity regulating kinase 4 promoted activation of the NLRP3 inflammasome-mediated pyroptosis in periodontitis

Inflammasomes in Alveolar Bone Loss

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