Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro
Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro
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DOI：
10.4049/jimmunol.1001284
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发表时间：
2011-02-15
影响因子：
4.4
通讯作者：
Busso, Nathalie
中科院分区：
文献类型：
--
作者：
Pazar, Borbala;Ea, Hang-Korng;Busso, Nathalie
碱性磷酸钙（BCP）晶体与严重的骨关节炎和急性关节周围炎症有关。已从病理组织中鉴定出三种主要形式的BCP晶体：磷酸八钙、碳酸盐取代的磷灰石和羟基磷灰石。我们研究了这些BCP晶体在体外的促炎作用，特别是在THP-1细胞、原代人单核细胞和巨噬细胞以及小鼠骨髓源性巨噬细胞（BMDM）中NLRP 3-炎性体的参与。用BCP晶体刺激的THP-1细胞以剂量依赖性方式产生IL-1 β。类似地，原代人细胞和野生型小鼠的BMDM在晶体刺激后也产生高浓度的IL-1 β。THP-1细胞转染短发夹RNA对NLRP 3炎性小体和小鼠BMDM的组件从缺乏NLRP 3，阿尔茨海默病相关的斑点样蛋白，或半胱天冬酶-1后BCP晶体刺激不产生IL-1 β。MTT法和流式细胞仪分析显示BCP晶体诱导巨噬细胞凋亡/坏死。总的来说，这些结果表明BCP晶体通过激活NLRP 3炎性体诱导IL-1 β分泌。此外，我们推测，IL-1阻断可能是一种新的策略，以抑制BCP诱导的炎症在人类疾病。免疫学杂志，2011，186：2495-2502。
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.