Article
Macrophages of patients with rheumatoid arthritis respond to extracellular calcium with an increased IL-1? production
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Authors
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Supriya Murthy
- Universität Leipzig, Rheumatologie, Leipzig
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Stefanie Raps
- Universität Leipzig, Rheumatologie, Leipzig
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Olga Seifert
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
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Christoph G. O. Baerwald
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
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Ulf Wagner
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
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Manuela Rossol
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
| Published: | February 5, 2019 |
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Outline
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Background: Monocytes and macrophages release high levels of cytokines during inflammatory responses. We have shown in previous studies that an increased extracellular calcium concentration is able to activate monocytes via G-protein-coupled receptors CaSR/GPRC6A. This results in the activation of the NLRP3 inflammasome and the production of IL-1βα and IL-18 but inflammasome-independent cytokines such as TNF and IL-6 are also secreted. Bone erosions and cell necrosis in patients with rheumatoid arthritis (RA) might lead to a local increase in extracellular calcium and contribute to the activation of monocytes/macrophages in the synovial tissue. Aim of the study was to analyze the cytokine response of calcium-induced activation of monocytes/macrophages in RA patients.
Methods: Monocytes were isolated from the peripheral blood of healthy controls and RA patients using magnetic separation (Miltenyi). The isolated monocytes were differentiated into macrophages using human serum or GM-CSF. Macrophages were then stimulated with Lipopolysaccharide in the presence of increased extracellular calcium. Cytokines were determined in the supernatant by ELISA.
Results: Macrophages from both healthy controls and RA patients released lower total amounts of IL-1b and IL-6 in comparison to monocytes but higher amounts of TNF. In addition, and in contrast to monocytes, extracellular calcium led to an increased IL-1β production but not to an increased TNF or IL-6 production in macrophages. Interestingly, macrophages already responded to much lower calcium concentrations than monocytes. Macrophages from RA patients released higher amounts of IL-1β when compared to age-matched healthy controls.
Conclusion: Macrophages are able to respond to much lower calcium concentrations than monocytes from the peripheral blood which might be an adaption to the lower calcium concentrations in the interstitial fluid of tissues (compared to serum). Macrophages from RA patients produce higher amounts of the inflammasome-dependent cytokine IL-1β and show, together with macrophages from healthy controls, a much more selective response to calcium than monocytes by only secreting inflammasome-dependent cytokines.
