Colony-stimulating factor-1 receptor blockade attenuates inflammation in inflamed gingival tissue explants.

Autor: Clark R; Department of Dental Medicine, Division of Oral diagnostics and Rehabilitation, Karolinska Institutet, Huddinge, Sweden., Lira-Junior R; Department of Dental Medicine, Division of Oral diagnostics and Rehabilitation, Karolinska Institutet, Huddinge, Sweden., Johannsen G; Department of Dental Medicine, Division of Oral Diseases, Karolinska Institutet, Huddinge, Sweden., Boström EA; Department of Dental Medicine, Division of Oral diagnostics and Rehabilitation, Karolinska Institutet, Huddinge, Sweden.; Department of Orofacial Medicine, Folktandvården Stockholms Län AB, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Journal of periodontal research [J Periodontal Res] 2021 Dec; Vol. 56 (6), pp. 1141-1153. Date of Electronic Publication: 2021 Sep 12.
DOI: 10.1111/jre.12926
Abstrakt: 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.
(© 2021 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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