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Complement 3 mediates periodontal destruction in patients with type 2 diabetes by regulating macrophage polarization in periodontal tissues.

ABSTRACT: OBJECTIVES:Diabetes aggravates the risk and severity of periodontitis, but the specific mechanism remains confused. Complement 3 (C3) is closely related to complications of type 2 diabetes (T2DM). In the present study, we concentrated on whether C3 mediates the development of periodontitis in T2DM. MATERIALS AND METHODS:Levels of C3 in blood and gingival crevicular fluid (GCF) of patients were measured first. A C3-knockout diabetic mouse model was established, real-time PCR, Western blotting and histological investigation were performed to evaluate the progress of periodontitis. Microcomputed tomography (micro-CT) and TRAP staining were performed to detect alveolar bone resorption. Immunofluorescence was performed to detect polarization of macrophages. RESULTS:Our data showed that C3 levels were elevated in the blood and GCF of T2DM patients compared with non-diabetic individuals. Increased C3 was closely related to the upregulation of inflammatory cytokines including interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-?), as well as the decline of the bone volume density (BMD) and bone volume over total volume (BV/TV) of the alveolar bones in diabetic mice. The deletion of C3 inhibited inflammatory cytokines and rescued the decreased BMD and BV/TV of the alveolar bones. C3-mediated polarization of macrophages was responsible for the damage. CONCLUSION:T2DM-related upregulation of C3 contributes to the development of periodontitis by promoting macrophages M1 polarization and inhibiting M2 polarization, triggering a pro-inflammatory effect on periodontal tissues.

SUBMITTER: Li Y

PROVIDER: S-EPMC7574872 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Complement 3 mediates periodontal destruction in patients with type 2 diabetes by regulating macrophage polarization in periodontal tissues.

Li Ye Y Wang Xinxin X Wang Saisai S Zhu Chunhui C Guo Jing J Li Ke K Li Ang A

Cell proliferation 20200814 10

<h4>Objectives</h4>Diabetes aggravates the risk and severity of periodontitis, but the specific mechanism remains confused. Complement 3 (C3) is closely related to complications of type 2 diabetes (T2DM). In the present study, we concentrated on whether C3 mediates the development of periodontitis in T2DM.<h4>Materials and methods</h4>Levels of C3 in blood and gingival crevicular fluid (GCF) of patients were measured first. A C3-knockout diabetic mouse model was established, real-time PCR, Weste ...[more]

PMID: 32794619

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Project description:Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J Lep db/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80+CD11b+CD86+) to anti-inflammatory M2 ones (F4/80+CD11b+CD206+) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4+ T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4+ T cells while promoting their differentiation into CD4+IL-4+ Th2 and CD4+Foxp3+ Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4+ T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.

Dataset Information

Complement 3 mediates periodontal destruction in patients with type 2 diabetes by regulating macrophage polarization in periodontal tissues.

Publications

Complement 3 mediates periodontal destruction in patients with type 2 diabetes by regulating macrophage polarization in periodontal tissues.

Similar Datasets

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