CD14(+) monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression


Brandt, D, Sohr, E, Pablik, J, Schnabel, A, Kapplusch, F, Maebert, K, Girschick, JH, Morbach, H, Thielemann, F, Hofmann, SR et al (show 1 more authors) (2018) CD14(+) monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression. CLINICAL IMMUNOLOGY, 196. pp. 77-84.

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Abstract

The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for “drivers” of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.

Item Type: Article
Uncontrolled Keywords: Bone and Bones, Monocytes, Humans, Bacterial Infections, Osteomyelitis, Chronic Disease, Inflammation, Blotting, Western, Case-Control Studies, DNA Methylation, Gene Expression Regulation, Interleukin-1beta, CARD Signaling Adaptor Proteins, Inflammasomes, Real-Time Polymerase Chain Reaction, NLR Family, Pyrin Domain-Containing 3 Protein, Lipopolysaccharide Receptors
Depositing User: Symplectic Admin
Date Deposited: 15 May 2018 09:23
Last Modified: 19 Jan 2023 06:33
DOI: 10.1016/j.clim.2018.04.011
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3021308
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