Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction.
Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction.
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DOI：
10.1186/s13075-014-0419-y
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发表时间：
2014-08-30
影响因子：
4.9
通讯作者：
Jones SA
中科院分区：
文献类型：
--
作者：
Greenhill CJ;Jones GW;Nowell MA;Newton Z;Harvey AK;Moideen AN;Collins FL;Bloom AC;Coll RC;Robertson AA;Cooper MA;Rosas M;Taylor PR;O'Neill LA;Humphreys IR;Williams AS;Jones SA
炎性体的激活与各种自身炎性和自身免疫性疾病的病理学有关。虽然NLRP 3炎性小体与关节炎进展有关，但对其滑膜调节或对关节组织病理学的贡献知之甚少。炎症激活的调节剂，如白细胞介素（IL）-10，可能有可能限制炎性小体驱动的关节炎疾病过程和相关的结构损伤。因此，我们使用IL-10缺陷（IL-10 KO）小鼠来评估NLRP 3炎性小体驱动的关节炎病理学。在IL-10 KO小鼠和野生型对照中建立抗原诱导的关节炎（AIA）。使用组织学和放射学方法结合滑膜mRNA的定量实时PCR研究，我们探索了炎症体组分的调节。这些与选择性阻断剂和破骨细胞分化测定中的离体调查研究相结合。在AIA中，IL-10 KO小鼠显示严重疾病，组织学和放射学关节评分增加。局灶性骨侵蚀与抗酒石酸酸性磷酸酶（TRAP）阳性细胞增加和IL-1β局部表达相关。当与对照相比时，IL-10 KO滑膜显示Illb、Il 33和NLRP 3炎性体组分的表达增加。滑膜Nlrp 3和Casp 1表达进一步与Acp 5（编码TRAP）相关，而对照小鼠中IL-10受体信号传导的中和导致Nlrp 3和Casp 1表达增加。在体外破骨细胞分化试验中，加入外源性IL-10或选择性阻断NLRP 3炎性小体可抑制破骨细胞生成。这些数据提供了IL-10、NLRP 3炎性小体的滑膜调节和炎性关节炎中观察到的骨侵蚀程度之间的联系。本文的在线版本（doi：10.1186/s13075-014-0419-y）包含补充材料，可供授权用户使用。
Activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential to limit the inflammasome-driven arthritic disease course and associated structural damage. Hence, we used IL-10-deficient (IL-10KO) mice to assess NLRP3 inflammasome-driven arthritic pathology. Antigen-induced arthritis (AIA) was established in IL-10KO mice and wild-type controls. Using histological and radiographic approaches together with quantitative real-time PCR of synovial mRNA studies, we explored the regulation of inflammasome components. These were combined with selective blocking agents and ex vivo investigative studies in osteoclast differentiation assays. In AIA, IL-10KO mice display severe disease with increased histological and radiographic joint scores. Here, focal bone erosions were associated with increased tartrate-resistant acid phosphatase (TRAP)-positive cells and a localized expression of IL-1β. When compared to controls, IL-10KO synovium showed increased expression of Il1b, Il33 and NLRP3 inflammasome components. Synovial Nlrp3 and Casp1 expression further correlated with Acp5 (encoding TRAP), while neutralization of IL-10 receptor signaling in control mice caused increased expression of Nlrp3 and Casp1. In ex vivo osteoclast differentiation assays, addition of exogenous IL-10 or selective blockade of the NLRP3 inflammasome inhibited osteoclastogenesis. These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis. The online version of this article (doi:10.1186/s13075-014-0419-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
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影响因子：
7.5
作者：
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通讯作者：
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影响因子：
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通讯作者：
Busso, Nathalie
影响因子：
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Kolly, Laeticia;Busso, Nathalie;So, Alexander
通讯作者：
So, Alexander
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作者：
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通讯作者：
Nowell, Mari