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Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200Rlow Monocyte-Derived Cells in Periodontitis.

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Bibliographic Details
Title: Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200Rlow Monocyte-Derived Cells in Periodontitis.
Authors: Björnfot Holmström, S., Clark, R., Zwicker, S., Bureik, D., Kvedaraite, E., Bernasconi, E., Nguyen Hoang, A.T., Johannsen, G., Marsland, B.J., Boström, E.A., Svensson, M.
Publication Year: 2025
Collection: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
Subject Terms: Adult, Antigens, Surface/biosynthesis, Surface/genetics, Surface/physiology, Cell Division, Cells, Cultured, Coculture Techniques, Cyclooxygenase Inhibitors/pharmacology, Epithelial Cells/metabolism, Fibroblasts/metabolism, Flow Cytometry, Gene Expression Regulation, Gingiva/enzymology, Gingiva/pathology, Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology, Humans, Inflammation, Keratinocytes/metabolism, Matrix Metalloproteinase 12/biosynthesis, Matrix Metalloproteinase 12/genetics, Matrix Metalloproteinase 12/physiology, Monocytes/enzymology, Monocytes/pathology, Periodontitis/enzymology, Periodontitis/pathology, Pyrazoles/pharmacology, Real-Time Polymerase Chain Reaction, Receptors
Description: Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD.
Document Type: article in journal/newspaper
Language: English
ISSN: 1550-6606
Relation: The Journal of Immunology; https://iris.unil.ch/handle/iris/218199; serval:BIB_6A43795EA9A1; 000417018100011
DOI: 10.4049/jimmunol.1700672
Availability: https://iris.unil.ch/handle/iris/218199
https://doi.org/10.4049/jimmunol.1700672
Accession Number: edsbas.D4BAFC7B
Database: BASE
Description
Abstract:Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD.
ISSN:15506606
DOI:10.4049/jimmunol.1700672