期刊
JOURNAL OF IMMUNOLOGY
卷 186, 期 4, 页码 2495-2502出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001284
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资金
- 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
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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