Dataset Information

IL-36? is a pivotal inflammatory player in periodontitis-associated bone loss.

ABSTRACT: Periodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1?, IL-6, TNF-? and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36?/IL-36?/IL-36?/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. We showed here that IL-36? mRNA gingival expression is higher in periodontitis patients, whereas IL-36? and IL-36Ra mRNA expression are lower compared to healthy controls. Interestingly, the elevated IL-36? expression in patients is positively correlated with the RANKL/OPG ratio, an index of bone resorption. In vitro, IL-36? expression was induced through TLR2 activation in primary OECs infected with P. gingivalis but not in gingival fibroblasts, the most widespread cell type in gingival connective tissue. In OECs, recombinant IL-36? enhanced the expression of inflammatory cytokines (IL-1?, IL-6, TNF-? and IL-36?), of TLR2 and importantly, the RANKL/OPG ratio. These findings suggest that IL-36? could be a pivotal inflammatory player in periodontitis by perpetuating gingival inflammation and its associated alveolar bone resorption and could be a relevant therapeutic target.

SUBMITTER: Cloitre A

PROVIDER: S-EPMC6917751 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-36γ is a pivotal inflammatory player in periodontitis-associated bone loss.

Cloitre Alexandra A Halgand Boris B Sourice Sophie S Caillon Jocelyne J Huck Olivier O Bugueno Isaac Maximiliano IM Batool Fareeha F Guicheux Jérôme J Geoffroy Valérie V Lesclous Philippe P

Scientific reports 20191217 1

Periodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1β, IL-6, TNF-α and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36α/IL-36β/IL-36γ/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. ...[more]

PMID: 31848404

Similar Datasets

Project description:BackgroundPeriodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive.ResultsExosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway.ConclusionIn conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos.

Dataset Information

IL-36? is a pivotal inflammatory player in periodontitis-associated bone loss.

Publications

IL-36γ is a pivotal inflammatory player in periodontitis-associated bone loss.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets