Journal
JOURNAL OF IMMUNOLOGY
Volume 186, Issue 4, Pages 2495-2502Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001284
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Funding
- Fonds National Suisse de La Recherche Scientifique [310030-130085/1, K-32K1-116460]
- Jean and Linette Warnery Foundation, Association pour Rhumatisme et Travail
- Association pour la Recherche en Pathologie Synoviale
- Association pour Cristaux et Cartilage
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Basic calcium phosphate (BCP) crystals are associated with severe osteoarthritis and acute periarticular inflammation. Three main forms of BCP crystals have been identified from pathological tissues: octacalcium phosphate, carbonate-substituted apatite, and hydroxyapatite. We investigated the proinflammatory effects of these BCP crystals in vitro with special regard to the involvement of the NLRP3-inflammasome in THP-1 cells, primary human monocytes and macrophages, and mouse bone marrow-derived macrophages (BMDM). THP-1 cells stimulated with BCP crystals produced IL-1 beta in a dose-dependent manner. Similarly, primary human cells and BMDM from wild-type mice also produced high concentrations of IL-1 beta after crystal stimulation. THP-1 cells transfected with short hairpin RNA against the components of the NLRP3 inflammasome and mouse BMDM from mice deficient for NLRP3, apoptosis-associated speck-like protein, or caspase-1 did not produce IL-1 beta after BCP crystal stimulation. BCP crystals induced macrophage apoptosis/necrosis as demonstrated by MTT and flow cytometric analysis. Collectively, these results demonstrate that BCP crystals induce IL-1 beta secretion through activating the NLRP3 inflammasome. Furthermore, we speculate that IL-1 blockade could be a novel strategy to inhibit BCP-induced inflammation in human disease. The Journal of Immunology, 2011, 186: 2495-2502.
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