Artikel
Pathologically Increased Ionized Calcium drives inflammation in rheumatoid arthritis through Calcium-sensing receptor-mediated NLRP3 inflammasome
Suche in Medline nach
Autoren
-
Supriya Murthy
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Elisabeth Jaeger
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Stefanie Raps
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Sebastian Jung
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Olga Seifert
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Christoph Baerwald
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Matthias Pierer
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Ulf Wagner
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
-
Manuela Rossol
- Leipzig University, Medical Clinic III, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Rheumatology, Leipzig
| Veröffentlicht: | 9. September 2020 |
|---|
Gliederung
Text
Introduction: A hallmark of the autoimmune disease rheumatoid arthritis (RA) is synovitis and the erosion of bone which might result in a local increase of extracellular calcium concentration. We have shown in previous studies that increased extracellular calcium activates the NLRP3 inflammasome of monocytes via G-protein-coupled receptors CaSR/GPRC6A. Aim of the study was to evaluate the contribution of extracellular calcium to local and systemic inflammatory responses in RA.
Methods: Magnetic separation was used to isolate monocytes from PBMCs of healthy donors, rheumatoid arthritis (RA), psoriatic arthritis (PsA) and Lupus (SLE) patients. The isolated monocytes were differentiated into macrophages using human serum. Cells were stimulated with lipopolysaccharide (LPS) and increased calcium concentrations (0.9-1.7mM) and cytokines were determined in the supernatant by ELISA. Arthritis was induced in 18 DBA/1 mice using collagen (CIA), 5 DBA/1 mice were used as controls.
Results: The ionized calcium concentration is increased in the synovial fluid of RA patients compared to control patients with psoriatic arthritis orankylosing spondylitis (1.1mM vs. 0.95mM, p=0.0004) while the ionized calcium concentration in the serum is not different. Monocytes of RA patients express significantly higher CaSR. Monocytes from RA patients responded with higher IL-1b, IL-1a and IL-18 production to an increased calcium concentration compared to healthy controls, PsA or SLE. Macrophages from RA patients released higher amounts of IL-1β when compared to age-matched healthy controls. Monocytes/macrophages in the collagen-induced arthritis mouse model showed similar results. The IL-1b production correlated with the CIA disease score (r=0.704, p=0.001).
Conclusion: The ionized calcium concentration is increased in the synovial fluid of RA patients. Monocytes/macrophages from RA patients and CIA mice respond with a higher cytokine production to ionized calcium. We propose that CaSR-mediated NLRP3 inflammasome activation contributes to the pathogenesis of RA.
Disclosures: None declared
