GM-CSF and uPA are required for Porphyromonas gingivalis-induced alveolar bone loss in a mouse periodontitis model

Immunology and Cell Biology
Roselind S LamEric C Reynolds

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and urokinase-type plasminogen activator (uPA) can contribute to the progression of chronic inflammatory diseases with possible involvement of macrophages. In this study, we investigated the role of both GM-CSF and uPA in Porphyromonas gingivalis-induced experimental periodontitis using GM-CSF-/- and uPA-/- mice. Intra-oral inoculation of wild-type (WT) C57BL/6 mice with P. gingivalis resulted in establishment of the pathogen in plaque and a significant increase in alveolar bone resorption. The infected mice also exhibited a CD11b(+) CD86(+) macrophage infiltrate into the gingival tissue, as well as P. gingivalis-specific pro-inflammatory cytokine and predominantly IgG2b antibody responses. In comparison, intra-oral inoculation of P. gingivalis did not induce bone resorption and there was significantly less P. gingivalis recovered from plaque in GM-CSF-/- and uPA-/- mice. Furthermore, P. gingivalis did not induce a macrophage gingival infiltrate or activate isolated peritoneal macrophages from the gene-deficient mice. Pro-inflammatory P. gingivalis-specific T-cell cytokine responses and serum interferon-gamma (IFN-γ) and IgG2b concentrations were significantly lower in G...Continue Reading

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Citations

Dec 30, 2016·Nature Reviews. Drug Discovery·John A HamiltonPaul P Tak
Jan 10, 2019·Journal of Clinical Periodontology·Reinhard Gruber
Oct 16, 2019·The Journal of Experimental Medicine·John A Hamilton
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alicja Sochaj-GregorczykJan Potempa
Mar 10, 2020·Journal of Periodontology·R Warren SandsDavid Mooney
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Jan 6, 2021·Journal of Periodontal Research·Ju Young JangSuk Ji
Oct 15, 2020·Journal of Clinical Periodontology·Nidhi MedaraIvan B Darby

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