Hypoxia and Porphyromonas gingivalis-lipopolysaccharide synergistically induce NLRP3 inflammasome activation in human gingival fibroblasts

Yang, Kai; Xu, Shuo; Zhao, Hongmei; Liu, Lingshuang; Lv, Xiaofang; Wang, Lei; Ji, Qiuxia

doi:10.1016/j.intimp.2021.107456

Cited by 33 publications

(32 citation statements)

References 42 publications

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“…High-dose glucose-treated P. gingivalis upregulates IL-1b and NLRP3 expression in human gingival fibroblasts (239). Notably, P. gingivalis-induced inflammasome activation may be associated with extracellular ATP and hypoxia in gingival epithelial cells and fibroblasts (171,(240)(241)(242)(243). However, conflicting evidence shows that P. gingivalis infection may also inhibit NLRP3 inflammasome activation in gingival epithelial cells and fibroblasts, resulting in the escape of these bacteria from host immune defense (244)(245)(246).…”

Section: Osteoporosismentioning

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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Section: Osteoporosismentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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“…Emerging evidence suggests that the NLRP3 inflammasome can react to a wide range of bacterial ligands, including LPS, bacterial RNA, and peptidoglycans (PAMPs or DAMPs), and plays a pivotal role in the pathogenesis of several diseases, such as rheumatoid arthritis, bone loss, osteomyelitis, periodontal disease, and others, by regulating the inflammatory response. Overexpression of NLRP3 exacerbates inflammatory osteolysis and inhibits calcium deposition in metabolic bone diseases [ 5 , 33 , 69 , 74 ]. In this sense, caspases have a close relationship with inflammasomes, once their activity triggers the caspase activation.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, HGFs stimulated with P. gingivalis LPS under hypoxia promoted caspase-1 activation and IL-1β maturation, while E. coli LPS also enhanced IL-1β maturation under normoxia [ 14 ]. Other In vitro research suggests that hypoxia can be used as an activation signal together with a “startup signal” of LPS to complete the entire pyroptosis pathway [ 14 , 74 ]. Furthermore, macrophages obtained from periodontitis patients were stimulated with E. coli LPS and P. gingivalis LPS while the expression of caspase-4 and IL-1β was seen for the cells stimulated with E. coli LPS [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis-Mediated Periodontal Disease

Sordi

Magini

Panahipour

et al. 2021

IJMS

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Pyroptosis is a caspase-dependent process relevant to the understanding of beneficial host responses and medical conditions for which inflammation is central to the pathophysiology of the disease. Pyroptosis has been recently suggested as one of the pathways of exacerbated inflammation of periodontal tissues. Hence, this focused review aims to discuss pyroptosis as a pathological mechanism in the cause of periodontitis. The included articles presented similarities regarding methods, type of cells applied, and cell stimulation, as the outcomes also point to the same direction considering the cellular events. The collected data indicate that virulence factors present in the diseased periodontal tissues initiate the inflammasome route of tissue destruction with caspase activation, cleavage of gasdermin D, and secretion of interleukins IL-1β and IL-18. Consequently, removing periopathogens’ virulence factors, triggering pyroptosis, is a potential strategy to combat periodontal disease and regain tissue homeostasis.

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“…In experimental periodontitis studies, the effects of hypoxia and LPS on NLP3 inflammasome activation were investigated. The synergistic effect of hypoxia and P. gingivalis-LPS induced IL-1 release stimulated an inflammatory response that would cause pyroptosis in human periodontal ligament fibroblasts [107]. P. gingivalis and E. coli LPS activated the inflammatory response and the caspase 1 cascade in gingival fibroblasts.…”

Section: Hypoxia In Local Inflammationmentioning

confidence: 98%

Vascular Changes and Hypoxia in Periodontal Disease as a Link to Systemic Complications

Çelik

Kantarcı

2021

Pathogens

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The hypoxic microenvironment caused by oral pathogens is the most important cause of the disruption of dynamic hemostasis between the oral microbiome and the immune system. Periodontal infection exacerbates the inflammatory response with increased hypoxia and causes vascular changes. The chronicity of inflammation becomes systemic as a link between oral and systemic diseases. The vascular network plays a central role in controlling infection and regulating the immune response. In this review, we focus on the local and systemic vascular network change mechanisms of periodontal inflammation and the pathological processes of inflammatory diseases. Understanding how the vascular network influences the pathology of periodontal diseases and the systemic complication associated with this pathology is essential for the discovery of both local and systemic proactive control mechanisms.

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Hypoxia and Porphyromonas gingivalis-lipopolysaccharide synergistically induce NLRP3 inflammasome activation in human gingival fibroblasts

Cited by 33 publications

References 42 publications

Inflammasomes in Alveolar Bone Loss

Inflammasomes in Alveolar Bone Loss

Pyroptosis-Mediated Periodontal Disease

Vascular Changes and Hypoxia in Periodontal Disease as a Link to Systemic Complications

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