HMGB1 Localization during Experimental Periodontitis

Nogueira, Andressa Vilas Boas; Souza, João Antônio Chaves de; Molon, Rafael Scaf de; Pereira, Elise de Matos; Aquino, Sabrina García de; Giannobile, William V.; Cirelli, Joni Augusto

doi:10.1155/2014/816320

Cited by 25 publications

(30 citation statements)

References 47 publications

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“…In addition, P. gingivalis is associated with oral squamous cell carcinomas and other chronic diseases [3, 52]. Our findings also support studies showing that HMGB1 is another possible candidate for an early inflammatory disease marker [53, 54]. Collectively, these results suggest that P. gingivalis NDK dampens the host-immune response by decreasing release of pro-inflammatory cytokine, IL-1β, and the pro-inflammatory danger signal, HMGB1, from infected GECs.…”

Section: Discussionsupporting

confidence: 87%

Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase

Johnson

Atanasova

Bui

et al. 2015

Microbes and Infection

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Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that Porphyromonas gingivalis, an intracellular opportunistic pathogen, uses a nucleoside-diphosphate kinase (NDK) homolog to inhibit innate immune responses due to stimulation by extracellular ATP, which acts as a danger signal that binds to P2X7 receptors and induces activation of an inflammasome and caspase-1. Thus, infection of gingival epithelial cells (GECs) with wild-type P. gingivalis results in inhibition of ATP-induced caspase-1 activation. However, ndk-deficient P. gingivalis is less effective than wild-type P. gingivalis in reducing ATP-mediated caspase-1 activation and secretion of the proinflammatory cytokine, IL-1β, from infected GECs. Furthermore, P. gingivalis NDK modulates release of high-mobility group protein B1 (HMGB1), a pro-inflammatory danger signal, which remains associated with chromatin in healthy cells. Unexpectedly, infection with either wild-type or ndk-deficient P. gingivalis causes release of HMGB1 from the nucleus to the cytosol. But HMGB1 is released to the extracellular space when uninfected GECs are further stimulated with ATP, and there is more HMGB1 released from the cells when ATP-treated cells are infected with ndk-deficient mutant than wild-type P. gingivalis. Our results reveal that NDK plays a significant role in inhibiting P2X7-dependent inflammasome activation and HMGB1 release from infected GECs.

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Section: Discussionsupporting

confidence: 87%

Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase

Johnson

Atanasova

Bui

et al. 2015

Microbes and Infection

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“…A single examiner, who was previously trained and calibrated and blind to the purpose of the experiment, performed the stereometric analysis using a point-counting technique. The following structures observed on each intersection point of the grid were recorded: fibroblastic (elongated morphology) cells, extracellular matrix, vascular structures, and inflammatory (rounded morphology) cells as described elsewhere [37]. The presence of each structure was expressed as a percentage of the total area analyzed in accordance with Liu et al [38] and Odze et al [39].…”

Section: Stereometric Analysismentioning

confidence: 99%

Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice

et al. 2015

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The ligature model was an effective approach to induce inflammation and bone loss similar to human periodontitis, but the oral gavage models were not efficient in inducing periodontal inflammation and tissue destruction in the conditions studied. Ligature models can provide a basis for future interventional studies that contribute to the understanding of the disease pathogenesis and the complex host response to microbial challenge.

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“…Recently, several reports have pointed out that HMGB1 is released in the gingival crevicular fluid from periodontitis patients and that TNF-␣ or butyric acid increases HMGB1 secretion in gingival epithelial cells in vitro (20,21). LPS and IL-1␤ increased HMGB1 secretion in periodontal ligament fibroblasts in vitro, and the number of HMGB1-positive cells was increased in a rat periodontitis model (22). Taking the data together, it has been considered that HMGB1 may be associated with the progression of periodontitis.…”

mentioning

confidence: 99%

Anti-HMGB1 Neutralizing Antibody Attenuates Periodontal Inflammation and Bone Resorption in a Murine Periodontitis Model

et al. 2018

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High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 mediates various inflammatory diseases, including periodontitis; however, the underlying mechanisms of HMGB1-induced periodontal inflammation are not completely understood. Here, we examined whether anti-HMGB1 neutralizing antibody inhibits periodontal progression and investigated the molecular pathology of HMGB1 and analysis indicated that HMGB1, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-1β (IL-1β) were secreted in response to tumor necrosis factor-α (TNF-α) stimuli in human gingival epithelial cells (HGECs) and human monocytic leukemia cells (THP-1) treated with phorbol myristate acetate. Increased levels of GM-CSF and IL-1β were observed in the conditioned media from TNF-α-stimulated HGECs and THP-1 Simultaneous stimulation with TNF-α and anti-HMGB1 antibody significantly decreased TNF-α-induced inflammatory cytokine secretion. Experimental periodontitis was induced in mice using-soaked ligatures. The extracellular translocation was confirmed in gingival epithelia in the periodontitis model mice by immunofluorescence analysis. Systemic administration of anti-HMGB1 neutralizing antibody significantly inhibited translocation of HMGB1. The anti-HMGB1 antibody inhibited periodontal inflammation, expression of IL-1β and C-X-C motif chemokine ligand 1 (CXCL1), migration of neutrophils, and bone resorption, shown by bioluminescence imaging of myeloperoxidase activity, quantitative reverse transcription-PCR (RT-PCR), and micro-computed tomography analysis. These findings indicate that HMGB1 is secreted in response to inflammatory stimuli caused by periodontal infection, which is crucial for the initiation of periodontitis, and the anti-HMGB1 antibody attenuates the secretion of a series of inflammatory cytokines, consequently suppressing the progression of periodontitis.

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HMGB1 Localization during Experimental Periodontitis

Cited by 25 publications

References 47 publications

Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase

Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase

Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice

Anti-HMGB1 Neutralizing Antibody Attenuates Periodontal Inflammation and Bone Resorption in a Murine Periodontitis Model

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