Langerhans cells down-regulate inflammation-driven alveolar bone loss.
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ABSTRACT:
SUBMITTER: Arizon M
PROVIDER: S-EPMC3344981 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Biochanin A (BA) is an organic compound produced by Trifolium pretense and Arachis hypogaea with anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis. Experimental rats (n=25) were distributed equally into five groups: i) Healthy control (control) group; ii) experimental periodontitis (ligation) group; and iii) and ligation plus low, medium and high dose of BA (12.5, 25 and 50 mg/kg/day, respectively) groups. A nylon ligature was inserted around rats' maxillary molars for 14 days to trigger the experimental periodontitis. BA was intravenous injected once daily for 4 weeks. After that, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and osteocalcin (OCN) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR. Alveolar bone volume was assessed via hematoxylin and eosin staining and micro-computed tomography. Osteoclasts were identified by tartrate-resistant acid phosphatase staining, and the level of the nuclear factor erythroid-2 related factor 2 (Nrf2) was also detected by immunohistochemical staining. BA treatment groups showed alleviated alveolar bone resorption compared with the ligation group. Moreover, BA treatment significantly inhibited IL-1β, TNF-α, ROS levels, and reduced leukocyte acid phosphatase-positive cells, as well as increased OCN and Nrf2 levels compared with the ligation group. BA had beneficial effects on experimental periodontitis of rats. BA treatment inhibited inflammation, regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss.
| S-EPMC7654219 | biostudies-literature
Project description:This study evaluated the effects of the chronic consumption of different concentrations of alcohol on the experimental periodontitis (EP). 160 rats were divided into 4 groups: (EP-NT) rats with EP and no alcohol exposure; (EP-A14) rats with EP exposed to 14% alcohol; (EP-A25) rats with EP exposed to 25% alcohol; (EP-A36) rats with EP exposed to 36% alcohol. The animals from the EP-A14, EP-A25 and EP-A36 groups were subjected to different concentrations of alcohol 30 days before EP induction. The histological characteristics, percentage of bone in the furcation (PBF) and bone metabolism in the furcation region were evaluated. The PBF and tartrate-resistant acid phosphatase (TRAP) data were subjected to statistical analysis. The EP-A14, EP-A25 and EP-A36 groups had lower PBFs compared with the EP-NT group. A more severe inflammatory process and a greater number of TRAP+ cells were also observed. In the EP-A14, EP-A25 and EP-A36 groups, the inflammatory process became more severe as the ingested alcoholic concentration increased. An increase in RANKL immunolabeling and a significantly higher number of TRAP+ cells were also observed. We conclude that chronic alcohol consumption increases the severity of experimental periodontitis in a dose-dependent manner by increasing the magnitude of local inflammatory responses and stimulating alveolar bone resorption.
| S-EPMC7446912 | biostudies-literature
Project description:SLIT2, a member of neuronal guidance cues, has been reported to regulate inflammation and cancer progression. Periodontitis is an oral inflammatory disease that degenerates periodontal tissue, alveolar bone and tooth. This study aims to explore the expression pattern of SLIT2 in periodontitis and its role in disease progression and bone loss. Gingival tissue of 20 periodontitis patients and 20 healthy-controls was obtained. Ligature-induced periodontitis (LIP) mice-model was developed in Slit2-Tg and wild-type mice. The effect of SLIT2 on inflammation, immune cell infiltration, M1 macrophage polarization, and alveolar bone loss in periodontitis was analyzed extensively. In periodontitis-affected gingival-tissue, SLIT2 expression was 4.4-fold higher compared to healthy-volunteers. LIP enhanced SLIT2 expression in mice periodontitis-affected periodontal tissue (PAPT) and blood circulation of wild-type mice by 4. 6-, and 5.0-fold, respectively. In Slit2-Tg-mice PAPT, SLIT2 expression was 1.8-fold higher compared to wild-type mice. Micro-CT and histomorphometric analysis revealed a 1.3-fold higher cement-enamel-junction to the alveolar-bone-crest (CEJ-ABC) distance and alveolar bone loss in LIP Slit2-Tg-mice compare to LIP wild-type mice. Results from RNA-sequencing, RT-qPCR, and ELISA showed a higher expression of Cxcr2, Il-18, TNF?, IL-6, and IL-1? in Slit2-Tg-mice PAPT compared to wild-type-mice. Slit2-Tg-mice PAPT showed a higher number of osteoclasts, M1 macrophages, and the upregulation of Robo1 expression. Slit2-Tg-mice PAPT showed upregulation of M1 macrophage marker CD16/32 and osteoclastogenic markers Acp5, Ctsk, and Nfatc1, but osteogenic markers (Alp, Bglap) remained unchanged. Immunohistochemistry unveiled the higher vasculature and infiltration of leucocytes and macrophages in Slit2-Tg-mice PAPT. RNA-sequencing, GO-pathway enrichment analysis, and western blot analysis revealed the activation of the MAPK signaling pathway in Slit2-Tg mice PAPT. In conclusion, SLIT2 overexpression in periodontitis intensifies inflammation, immune cells infiltration, M1 macrophage polarization, osteoclastogenesis, and alveolar bone loss, possibly via activation of MAPK signaling, suggesting the role of SLIT2 on exacerbation of periodontitis and alveolar bone loss.
| S-EPMC7371784 | biostudies-literature
Project description:Alveolar epithelium plays a pivotal role in protecting the lungs from inhaled infectious agents. Therefore, the regenerative capacity of the alveolar epithelium is critical for recovery from these insults in order to rebuild the epithelial barrier and restore pulmonary functions. Here, we show that sublethal infection of mice with Streptococcus pneumoniae, the most common pathogen of community-acquired pneumonia, led to exclusive damage in lung alveoli, followed by alveolar epithelial regeneration and resolution of lung inflammation. We show that surfactant protein C-expressing (SPC-expressing) alveolar epithelial type II cells (AECIIs) underwent proliferation and differentiation after infection, which contributed to the newly formed alveolar epithelium. This increase in AECII activities was correlated with increased nuclear expression of Yap and Taz, the mediators of the Hippo pathway. Mice that lacked Yap/Taz in AECIIs exhibited prolonged inflammatory responses in the lung and were delayed in alveolar epithelial regeneration during bacterial pneumonia. This impaired alveolar epithelial regeneration was paralleled by a failure to upregulate I?Ba, the molecule that terminates NF-?B-mediated inflammatory responses. These results demonstrate that signals governing resolution of lung inflammation were altered in Yap/Taz mutant mice, which prevented the development of a proper regenerative niche, delaying repair and regeneration of alveolar epithelium during bacterial pneumonia.
| S-EPMC6486331 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVE:Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH)2 D3 , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD). MATERIALS AND METHODS:Wild-type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH)2 D3 , followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2 D3 was quantified by ELISA. Effect of vitamin D on basal IL-1? expression in mice was determined by topical administration to the gingiva of wild-type mice, followed by qRT-PCR. RESULTS:Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH)2 D3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25-hydroxylases (CYP27A1 and CYP2R1), as well as 1-? hydroxylase, enabling conversion of vitamin D to both 25(OH)D3 and 1,25(OH)2 D3 . Topical application of both vitamin D3 and 1,25(OH)2 D3 to the gingiva of mice led to rapid inhibition of IL-1? expression, a prominent pro-inflammatory cytokine associated with inflammation, which also exhibited more than a 2-fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH)2 D3 treatment, as determined by RNA-seq. CONCLUSION:Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease.
| S-EPMC6626553 | biostudies-literature
Project description:Periodontitis is very prevalent worldwide and is one of the major causes of tooth loss in adults. About 80% of the worldwide population use medicinal plants for their health care. Stemodia maritima L. (S. maritima) antioxidant and antimicrobial effects in vitro as well as anti-inflammatory properties. Herein, the potential therapeutic effect of S. maritima was assessed in rats subjected to experimental periodontitis (EP). EP was induced in female Wistar rats by nylon thread ligature around 2nd upper left molars for 11 days. Animals received (per os) S. maritima (0.2; 1 or 5 mg/kg) or vehicle (saline + DMSO) 1 h before ligature and then once daily for 11 days. The naive group had no manipulation. After this time-point, the animals were terminally anesthetized, and the maxillae were removed for morphometric and histological analyzes (HE). Gingival tissues were dissected to cytokine levels detection (TNF-?, IL1-?, CINC-1, and IL-10), enzymes superoxide dismutase (SOD), and catalase (CAT) analysis, as well as gene expression (TNF-?, IL-1?, RANK, and iNOS) by qRT-PCR. Systemic parameters (weight variation, plasma levels of hepatic enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatinine, total alkaline phosphatase (TALP), and bone alkaline phosphatase (BALP) were performed. Histological analysis of the stomach, liver, kidney, and heart was also performed. S. maritima (5 mg/kg) decreased alveolar bone loss, TNF-? and CINC-1 gingival levels, oxidative stress, and transcription of TNF-?, IL1-?, RANK, and iNOS genes. It elevated both BALP activity and IL-10 gingival levels. The animals showed no any signs of toxicity. In conclusion, S. maritima reduced pro-inflammatory cytokine production, oxidative stress, and alveolar bone loss in a pre-clinical trial of periodontitis. S. maritima is a potential tool for controlling the development of periodontitis.
| S-EPMC5717945 | biostudies-literature
Project description:Background and objectivePeri-implantitis and periodontitis are different entities in immune characteristics even though they share similar features in clinical and radiologic signs. Toll-like receptor 2 (TLR-2), one of the key pathogen-recognition receptors in the innate immune system, plays an important role in the progression of periodontitis. However, the role of TLR-2 in peri-implantitis remains unclear. The objective of this study was to investigate the role of TLR-2 in inflammation and alveolar bone loss in a murine model of ligature-induced peri-implantitis and to compare it with ligature-induced periodontitis.Material and methodsSmooth-surface titanium implants were placed in the alveolar bone of the left maxillary molars of wild-type (WT) and Tlr2 knockout (Tlr2-KO) mice 6 weeks after tooth extraction. Silk ligatures were applied to the left implant fixtures and the right maxillary second molars to induce peri-implantitis and periodontitis 4 weeks after implant placement. Two weeks after ligation, bone loss around the implants and maxillary second molars was analysed by micro-computed tomography (micro-CT), and inflammation around the implants and maxillary second molars was assessed at the same time point using histology and TRAP staining, respectively. Expression of mRNA for proinflammatory cytokines (interleukin-1β [Il1β], tumor necrosis factor-α [Tnfα]), an anti-inflammatory cytokine (interleukin-10 [Il10]) and osteoclastogenesis-related cytokines (Rankl, osteoprotegerin [Opg]) were evaluated, in gingival tissue, using real-time quantitative PCR (RT-qPCR).ResultsThe success rate of implant osseointegration was significantly higher in Tlr2-KO mice (85.71%) compared with WT mice (53.66%) (P = .0125). Micro-CT revealed significantly decreased bone loss in Tlr2-KO mice compared with WT mice (P = .0094) in peri-implantitis. The levels of mRNA for Il1β (P = .0055), Tnfα (P = .01) and Il10 (P = .0019) in gingiva were significantly elevated in the peri-implantitis tissues of WT mice, but not in Tlr2-KO mice, compared with controls. However, the gingival mRNA ratios of Rankl/Opg in peri-implant tissues were significantly upregulated in both WT (P = .0488) and Tlr2-KO (P = .0314) mice. Ligature-induced periodontitis exhibited similar patterns of bone loss and inflammatory cytokine profile in both groups of mice, except that the level of Il10 was elevated (P = .0114) whereas the Rankl/Opg ratio was not elevated (P = .9755) in Tlr2-KO mice compared with control mice. Histological findings showed increased numbers of TRAP-positive cells and infiltrated inflammatory cells in ligature-induced peri-implantitis in both WT (P < .01) and Tlr2-KO mice (P < .05), and the numbers of both types of cell were significantly higher in WT mice than in Tlr2-KO mice (P < .01).ConclusionThis study suggests that TLR-2 mediates bone loss in both peri-implantitis and periodontitis. However, different molecular features may exist in the pathogenesis of the two diseases.
| S-EPMC5760345 | biostudies-literature
Project description:The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1?, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis.
| S-EPMC4959623 | biostudies-literature
Project description:ObjectivesOestrogen deficiency is an aetiological factor of postmenopausal osteoporosis (PMO), which not only decreases bone density in vertebrae and long bone but also aggravates inflammatory alveolar bone loss. Recent evidence has suggested the critical role of gut microbiota in osteoimmunology and its influence on bone metabolisms. The present study aimed to evaluate the therapeutic effects of probiotics on alveolar bone loss under oestrogen-deficient condition.Materials and methodsInflammatory alveolar bone loss was established in ovariectomized (OVX) rats, and rats were daily intragastrically administered with probiotics until sacrifice. Gut microbiota composition, intestinal permeability, systemic immune status and alveolar bone loss were assessed to reveal the underlying correlation between gut microbiota and bone metabolisms.ResultsWe found administration of probiotics significantly prevented inflammatory alveolar bone resorption in OVX rats. By enriching butyrate-producing genera and enhancing gut butyrate production, probiotics improved intestinal barrier and decreased gut permeability in the OVX rats. Furthermore, the oestrogen deprivation-induced inflammatory responses were suppressed in probiotics-treated OVX rats, as reflected by reduced serum levels of inflammatory cytokines and a balanced distribution of CD4+ IL-17A+ Th17 cells and CD4+ CD25+ Foxp3+ Treg cells in the bone marrow.ConclusionsThis study demonstrated that probiotics can effectively attenuate alveolar bone loss by modulating gut microbiota and further regulating osteoimmune response and thus represent a promising adjuvant in the treatment of alveolar bone loss under oestrogen deficiency.
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Project description:Recruitment of innate immune effector cells into sites of infection is a critical component of resistance to pathogen infection. Using a model of intradermal footpad injection of Candida albicans, we observed that inflammation as measured by footpad thickness and neutrophil recruitment occurred independent of adoptive immunity but was significantly reduced in MyD88(-/-) and IL-6(-/-) mice. Unexpectedly, huLangerin-DTA mice (?LC) that lack Langerhans cells (LC) developed increased skin inflammation and expressed higher amounts of IL-6, suggesting a suppressive role for LC. Increased inflammation also occurred in Rag1(-/-) ?LC mice but was reversed by Ab-mediated ablation of NK cells. CXCR6(+)CD49a(+) NK cells are a liver-resident subset that can mediate inflammatory skin responses. We found that exaggerated skin inflammation was absent in ?LC × CXCR6(-/-) mice. Moreover, the exaggerated response in ?LC mice could be adoptively transferred with liver CD49a(+) NK cells. Finally, CD49a(+) NK cells in ?LC but not control mice were recruited to the skin, and inhibition of their recruitment prevented the exaggerated response. Thus, in the absence of LC, CD49a(+) liver NK cells display an inappropriately proinflammatory phenotype that results in increased local skin inflammation. These data reveal a novel function for LC in the regulation of this recently described subset of skin tropic NK cells.
| S-EPMC4546924 | biostudies-literature