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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3
1Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.
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.
Insights
Monocytes play a key role in chronic nonbacterial osteomyelitis (CNO) inflammation. Increased NLRP3 inflammasome activation in monocytes, linked to DNA hypomethylation, suggests they are crucial drivers of this bone disease.
Area of Science:
- Immunology
- Genetics
- Pathophysiology
Background:
- Chronic nonbacterial osteomyelitis (CNO) pathophysiology is not fully understood.
- Increased NLRP3 inflammasome activation and IL-1β release in monocytes are implicated in CNO bone inflammation.
Purpose of the Study:
- To investigate the role of immune cell infiltrates, particularly monocytes, in CNO across different disease stages.
- To explore the link between inflammasome component expression, DNA methylation, and monocyte involvement in CNO.
Main Methods:
- Analysis of immune cell infiltrates in CNO bone lesions.
- Assessment of inflammasome component (NLRP3, ASC) gene expression in monocytes.
- DNA methylation analysis of NLRP3 and PYCARD genes in monocytes.
Main Results:
- Monocytes are consistently involved in CNO at all disease stages, unlike other immune cells.
- Increased expression of NLRP3 and ASC inflammasome components was observed in monocytes.
- Site-specific DNA hypomethylation around NLRP3 and PYCARD genes correlated with increased inflammasome component expression.
Conclusions:
- Pro-inflammatory monocytes are central to CNO pathophysiology.
- Monocyte-derived NLRP3 inflammasome activation, potentially driven by DNA hypomethylation, contributes to bone inflammation in CNO.
- Identified cellular and molecular alterations in monocytes may serve as potential biomarkers or therapeutic targets for CNO.
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