Colony‐stimulating factor‐1 receptor blockade attenuates inflammation in inflamed gingival tissue explants
| Autor: | Reuben Clark, Ronaldo Lira-Junior, Gunnar Johannsen, Elisabeth A. Boström |
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| Rok vydání: | 2021 |
| Předmět: |
Inflammation
Macrophage colony-stimulating factor education.field_of_study medicine.diagnostic_test business.industry Population Gingiva Peripheral blood mononuclear cell Monocytes Colony stimulating factor 1 receptor Colony-Stimulating Factors Western blot Leukocytes Mononuclear Interleukin 34 Cancer research Humans Periodontics Immunohistochemistry Medicine medicine.symptom education business |
| Zdroj: | Journal of Periodontal Research. 56:1141-1153 |
| ISSN: | 1600-0765 0022-3484 |
| Popis: | Background and objective Colony-stimulating factor-1 receptor (CSF-1R) regulates myeloid cell function and mediates osteoclastogenesis. CSF-1R blockade has been suggested as a potential therapeutic target to halt inflammation and bone resorption; however, the expression and function of CSF-1R in human gingiva is yet unknown. Methods Gingival tissue was collected from 22 non-periodontitis controls and 31 periodontitis (PD) patients. CSF-1R expression in gingival tissue was assessed with q-PCR, western blot, and immunohistochemistry (IHC). Cell surface expression of CSF-1R was analyzed by flow cytometry. The effects of CSF-1R inhibition on the production of inflammatory mediators by inflamed gingival tissue explants and peripheral blood mononuclear cells (PBMCs) were assessed with a bead-based multiplex array and ELISA. Results CSF-1R protein expression was increased in gingival tissue from PD patients compared with controls as assessed with western blot (1.5-fold increase) and IHC (4.5-fold increase). Similar proportions of HLA-DR+ CD64+ cells and comparable CSF-1R expression in this cell population were found in gingival tissue from PD patients and controls. In peripheral blood monocytes, CSF-1R was predominantly expressed by non-classical and intermediate monocytes. Targeting CSF-1R in gingival tissue explants attenuated the production of MMP-1, MMP-2, MMP-12, and MMP-13. The blocking in PBMCs attenuated the production of IL-8 and MMP-9. Conclusion These results indicate that CSF-1R is elevated in PD, and its inhibition attenuates inflammatory mediators in the inflamed gingival tissue and circulating myeloid cells. Together these findings suggest that CSF-1R might be involved in regulating inflammatory processes in PD, and a potential therapeutic target to reduce the harmful inflammation. |
| Databáze: | OpenAIRE |
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