Macrophage immunomodulation in chronic osteolytic diseases—the case of periodontitis

Sima, Corneliu; Viniegra, Ana; Glogauer, Michael

doi:10.1002/jlb.1ru0818-310r

Cited by 75 publications

(93 citation statements)

References 190 publications

(410 reference statements)

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“…Our laboratory and others have shown that LPS increases ASMase‐mediated SM hydrolysis and CER production by stimulating ASMase activity, leading to an increase in inflammatory response of macrophages (Jin et al, ; Sakata et al, ). Given the importance of macrophages in periodontitis (Sima, Viniegra, & Glogauer, ), these findings suggest that ASMase may mediate LPS‐induced periodontitis, and it is thus expected that ASMase deficiency would reduce LPS‐triggered periodontitis. However, the result of this study is unexpected as it showed that ASMase deficiency exacerbated LPS‐induced periodontitis in animal model.…”

Section: Discussionmentioning

confidence: 79%

Acid sphingomyelinase deficiency exacerbates LPS‐induced experimental periodontitis

Zhang

et al. 2020

Oral Diseases

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Background Mutation of the gene for acid sphingomyelinase (ASMase) causes Niemann–Pick disease. However, the effect of ASMase deficiency on periodontal health is unknown. Periodontal disease is a disease resulting from infection and inflammation of periodontal tissue and alveolar bone that support the teeth. The goal of this study was to determine the role of ASMase deficiency in periodontal inflammation and alveolar bone loss. Methods We induced periodontitis in wild‐type and ASMase‐deficient (ASMase−/−) mice with periodontal lipopolysaccharide (LPS) injection and compared the alveolar bone loss and periodontal inflammation between these mice. Results Results showed that ASMase deficiency did not significantly change metabolic parameters, but exacerbated LPS‐induced alveolar bone loss, osteoclastogenesis, and periodontal tissue inflammation. To understand the mechanisms by which ASMase deficiency aggravates LPS‐induced periodontitis, we analyzed sphingolipids in periodontal tissues. Results showed that ASMase deficiency led to increases in not only sphingomyelin, but also ceramide (CER), a bioactive sphingolipid known to promote inflammation. Results further showed that ASMase deficiency increased CER de novo synthesis. Conclusion ASMase deficiency exacerbated LPS‐induced alveolar bone loss and periodontal inflammation. ASMase deficiency leads to an unexpected CER increase by stimulating de novo synthesis CER, which is likely to be involved in the ASMase deficiency‐exacerbated periodontitis.

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Section: Discussionmentioning

confidence: 79%

Acid sphingomyelinase deficiency exacerbates LPS‐induced experimental periodontitis

Zhang

et al. 2020

Oral Diseases

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“…The monocyte-macrophage plays an important role both in the adaptive immune response and innate immunity [6]. Plenty of evidences show that macrophages derived from circulating mononuclear cells and tissue resident cells exist in the diseased tissues of periodontitis and are leading players in immunoreaction against periodontal pathogens, contributing to the initiation of periodontal inflammation [7,8]. The number of macrophages and macrophagessecreted pro-inflammatory cytokines including IL-1, IL-8, TNF-α and so on are elevated in periodontitis-associated gingival tissue biopsies [9].…”

Section: Introductionmentioning

confidence: 99%

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

et al. 2020

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Background: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide (LPS)-induced macrophage M1 polarization and clarify the underlying mechanisms. Methods: RAW264.7 cells were polarized to M1 macrophage by LPS with or without recombinant PGRN (rPGRN) and tumor necrosis factor alpha antibody (anti-TNF-α). A cell counting kit-8 assay (CCK-8), flow cytometry, Quantitative Real-Time PCR assay (q-PCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) were used to determine the effect of different treatments on cell proliferation, expression of surface phenotype marker and expressions and secretion of inflammatory cytokines. The activation of NF-κB/mitogen-activated protein kinase (MAPK) pathways and the nuclear translocation of NF-κB p65 were detected by Western blot and immunofluorescence respectively. THP-1 and primary bone marrow-derived monocytes (BMDMs) were also used to demonstrate effect of PGRN on expressions and secretion of inflammatory cytokines induced by LPS. Results: In RAW264.7 cells, rPGRN at concentrations below 80 ng/ml significantly promoted cell proliferation in dose dependent fashion. rPGRN significantly inhibited LPS-induced change of phenotype (CD86/CD206 ratio) and function (tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) expressions). LPS-stimulated secretion of TNF-α and activated phosphorylation of IKKα/β, IкBα, p65, JNK and p38 and the nucleus translocation of NF-кB p65 were also significantly downregulated by rPGRN. In addition, recombinant TNF-α (rTNF-α) significantly boosted TNF-α and iNOS expression vs the control group. Moreover, anti-TNF-α significantly inhibited LPS-induced TNF-α and iNOS expression. In THP-1 and BMDM cells, reversing effect of rPGRN on LPS-enhanced expressions of TNF-α and iNOS and secretion of TNF-α was further demonstrated.

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“…Whereas CXCL1 is a strong chemoattractant for neutrophils, CCL2 and CCL5 mainly promote the recruitment of monocytes, macrophages, and lymphocytes [13]. Several studies have clearly demonstrated that these cell types and their subsets have defined roles in the battle between the host and microorganisms in periodontitis [21,22].…”

Section: Discussionmentioning

confidence: 99%

CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies

et al. 2020

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Objectives This study was established to investigate whether the chemokines CXCL1, CCL2, and CCL5 are produced in periodontal cells and tissues and, if so, whether their levels are regulated by microbial and/or mechanical signals. Materials and methods The chemokine expression and protein levels in gingival biopsies from patients with and without periodontitis were analyzed by RT-PCR and immunohistochemistry. The chemokines were also analyzed in gingival biopsies from rats subjected to experimental periodontitis and/or orthodontic tooth movement. Additionally, chemokine levels were determined in periodontal fibroblasts exposed to the periodontopathogen Fusobacterium nucleatum and mechanical forces by RT-PCR and ELISA. Results Higher CXCL1, CCL2, and CCL5 levels were found in human and rat gingiva from sites of periodontitis as compared with periodontally healthy sites. In the rat experimental periodontitis model, the bacteria-induced upregulation of these chemokines was significantly counteracted by orthodontic forces. In vitro, F. nucleatum caused a significant upregulation of all chemokines at 1 day. When the cells were subjected simultaneously to F. nucleatum and mechanical forces, the upregulation of chemokines was significantly inhibited. The transcriptional findings were paralleled at protein level. Conclusions This study provides original evidence in vitro and in vivo that the chemokines CXCL1, CCL2, and CCL5 are regulated by both microbial and mechanical signals in periodontal cells and tissues. Furthermore, our study revealed that biomechanical forces can counteract the stimulatory actions of F. nucleatum on these chemokines. Clinical relevance Mechanical loading might aggravate periodontal infection by compromising the recruitment of immunoinflammatory cells.

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Macrophage immunomodulation in chronic osteolytic diseases—the case of periodontitis

Cited by 75 publications

References 190 publications

Acid sphingomyelinase deficiency exacerbates LPS‐induced experimental periodontitis

Acid sphingomyelinase deficiency exacerbates LPS‐induced experimental periodontitis

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies

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