Université de Strasbourg, INSERM, ImmunoRhumatologie Moléculaire UMR_S 1109, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, F-67000 Strasbourg, France.
Fédération Hospitalo-Universitaire, OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, 67085 Strasbourg, France.
Theranostics. 2020 Jan 12;10(5):2158-2171. doi: 10.7150/thno.40650. eCollection 2020.
: The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1β in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1β secretion , the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. : Acute urate crystal inflammation was obtained by subcutaneous injections of MSU crystals in mice. Symptoms were followed by scoring, cytokine quantification by ELISA and western blot, gene expression by RT-qPCR and RNAseq; Magnetic Resonance Imaging was also used to assess inflammation. : We provide an extensive clinical, biological and molecular characterization of an acute uratic inflammation mouse model which accurately mimics human gout. We report the efficacy of topical imiquimod treatment and its impact on Interferon-dependent down modulation of gene expression in this experimental model. : Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities for gout patients.
: 单钠尿酸盐（MSU）晶体在痛风病理生理学中的作用已得到充分描述，白细胞介素 1β（IL-1β）在构成该疾病特征的炎症反应中的主要作用也已得到充分描述。然而，尽管已经发现了 NLRP3 炎性体及其作为连接危险信号（MSU）检测与 IL-1β 分泌的模式识别受体的作用，导致痛风患者关节炎症的确切机制仍知之甚少。 : 通过向小鼠皮下注射 MSU 晶体来获得急性尿酸晶体炎症。通过评分、ELISA 和 Western blot 定量细胞因子、RT-qPCR 和 RNAseq 检测基因表达以及磁共振成像来监测症状。 : 我们提供了一种急性尿酸炎症小鼠模型的广泛临床、生物学和分子特征描述，该模型准确模拟了人类痛风。我们报告了局部咪喹莫特治疗的疗效及其对这种实验模型中干扰素依赖性下调基因表达的影响。 : 我们的工作揭示了 MSU 依赖性炎症的几个关键特征，并为痛风患者确定了新的治疗机会。
