| Octacalcium phosphate (OCP) crystals induce inflammation in vivo through IL-1 but independent of the NLRP3 inflammasome. | |
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MedLine Citation:
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PMID: 21080360 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE:: To determine the mechanisms involved in inflammatory responses against octacalcium phosphate (OCP) crystals in vivo METHODS:: OCP crystal-induced inflammation was monitored using a peritoneal model of inflammation in mice with different deficiencies affecting interleukin-1 (IL-1) secretion (IL-1α(-/-), IL-1β(-/-), ASC(-/-)and NLRP3-/- mice), or in mice pre-treated with IL-1 inhibitors (anakinra and anti-IL-1β). The production of IL-1α, IL-1β and myeloid-related protein 8 and myeloid-related protein 14 complexes (MRP8-MRP14) was determined by ELISA. Peritoneal neutrophil recruitment and cell viability were determined by flow cytometry. Depletion of mast cells or resident macrophages was performed by pre-treatment with compound 48/80 or clodronate liposomes, respectively. RESULTS:: OCP crystals induced peritoneal inflammation as demonstrated by neutrophil recruitment and up-modulation of IL-1α, IL-1β, and MRP8-MRP14, to levels comparable to monosodium urate monohydrate (MSU) crystals. This OCP crystal-induced inflammation was both IL-1α- and IL-1β-dependent as shown by the inhibitory effects of anakinra (IL-1Ra) and anti-IL-1β antibody treatment. Accordingly, OCP crystal stimulation resulted in milder inflammation in IL-1α(-/-) and IL-1β(-/-) mice. Interestingly, ASC(-/-) and NLRP3(-/-) mice did not show any alteration in their inflammatory status in response to OCP crystals. Depletion of the resident macrophage population resulted in a significant decrease in crystal-induced neutrophil infiltration and proinflammatory cytokine production in vivo, whereas mast cell depletion had no effect. Finally, we demonstrate that OCP crystals induce apoptosis/necrosis of peritoneal cells in vivo. CONCLUSION:: These data indicate that macrophages, rather than mast cells, are important for initiating and driving OCP crystal-induced inflammation. Additionally, OCP crystals induce IL-1 dependent peritoneal inflammation, without NLRP3 inflammasome requirement. |
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Authors:
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Sharmal Narayan; Borbola Pazar; Hang-Korng Ea; Laeticia Kolly; Nathaliane Bagnoud; Véronique Chobaz; Frédéric Lioté; Thomas Vogl; Dirk Holzinger; Alexander Kai-Lik So; Nathalie Busso |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-11-15 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Rheumatology, Département de l'appareillocomoteur (DAL), Centre HospitalierUniversitaireVaudois (CHUV) and University of Lausanne, Lausanne, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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