Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro

Journal of Immunology - Tập 186 Số 4 - Trang 2495-2502 - 2011
Borbála Pazár1, Jean‐Claude Roujeau2,3, Sharmal Narayan1, Laeticia Kolly1, Nathalie Bagnoud1, Véronique Chobaz1, Thierry Roger4, Frédéric Lioté2,3, Alexander So1, Nathalie Busso1
1*Department of Rheumatology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland;
2†Unité Mixte de Recherche S606, INSERM, Lariboisière Hospital, 75010 Paris, France; and
3‡Institut Claude Bernard-IFR2, Université Paris–Diderot, Faculté de Medicine, 75890 Paris Cedex 18, France
4§Infectious Diseases Service, Department of Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

Tóm tắt

Abstract 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-1β in a dose-dependent manner. Similarly, primary human cells and BMDM from wild-type mice also produced high concentrations of IL-1β 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-1β 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-1β 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.

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