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Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis
Veterinary Immunology and Immunopathology ( IF 1.8 ) Pub Date : 2021-09-21 , DOI: 10.1016/j.vetimm.2021.110325
Marie Walters 1 , Kerstin Skovgaard 2 , Pia Haubro Andersen 3 , Peter M H Heegaard 4 , Stine Jacobsen 1
Affiliation  

The role of resident cells such a synoviocytes and chondrocytes in intra-articular inflammation is well-characterized, however the in vivo gene expression patterns of cells (predominantly leukocytes) in the synovial fluid (SF) of an inflamed joint have never previously been investigated. The aim of this study was to investigate gene expression in SF leukocytes from the inflamed joint cavity after intra-articular lipopolysaccharide (LPS) injection in horses to improve our understanding of the temporal regulation of the intra-articular inflammatory response. Gene expression was investigated in SF samples available from six horses 2, 4, 8 16 and 24 h after experimental induction of inflammation in the radiocarpal joint by lipopolysaccharide (LPS) injection. Leukocytic expression of 43 inflammation-related genes was studied using microfluidic high throughput qPCR (Fluidigm®). Expression of 26 genes changed significantly over the 24 h study period, including pro- and anti-inflammatory genes such as interleukin (IL)1, IL6, tumor necrosis factor (TNF), cyclooxygenase 2 (COX2), IL1 receptor antagonist (IL1RN), IL10, and superoxide dismutase 2 (SOD2), chemokine genes, apoptosis-related genes, and genes related to cartilage turnover (matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1). The inflammatory responses appeared to be regulated, as an early increase (at 2 h) in expression of the pro-inflammatory genes IL1, IL6, TNF and COX2 was rapidly followed by increased expression (at 4 h) of several anti-inflammatory genes (IL10, IL1RN and SOD2). Similarly, both pro- and anti-apoptotic gene expression as well as expression of chondrodegenerative and chondroprotective genes were activated in SF leukocytes. Thus, the inflammatory response in leukocytes infiltrating the joint in the acute stage of arthritis was well orchestrated in this single-hit LPS-induced arthritis model. This study is the first to describe gene expression patterns in SF-derived leukocytes in vivo during severe joint inflammation, and the results thus expand our knowledge of basic inflammatory mechanisms in the early local response in an inflamed joint.



中文翻译:

脂多糖诱导性关节炎马滑液白细胞局部基因调控动力学

常驻细胞(如滑膜细胞和软骨细胞)在关节内炎症中的作用已得到充分表征,但在体内以前从未研究过发炎关节的滑液(SF)中细胞(主要是白细胞)的基因表达模式。本研究的目的是研究马关节内脂多糖 (LPS) 注射后发炎关节腔 SF 白细胞中的基因表达,以提高我们对关节内炎症反应时间调节的理解。在通过脂多糖 (LPS) 注射实验性诱导桡腕关节炎症后 2、4、8、16 和 24 小时,在来自六匹马的 SF 样品中研究基因表达。使用微流控高通量 qPCR (Fluidigm®) 研究了 43 个炎症相关基因的白细胞表达。在 24 小时研究期间,26 个基因的表达发生了显着变化,IL)1、IL6、肿瘤坏死因子 ( TNF )、环氧合酶 2 ( COX2 )、IL1 受体拮抗剂 ( IL1RN )、IL10和超氧化物歧化酶 2 ( SOD2 )、趋化因子基因、凋亡相关基因和与软骨更新相关的基因(基质金属蛋白酶 8 和金属蛋白酶组织抑制剂 1)。炎症反应似乎受到调节,因为促炎基因IL1、IL6、TNFCOX2表达的早期增加(在 2 小时时)随后是几种抗炎基因的表达增加(在 4 小时时)。IL10、IL1RNSOD2)。类似地,促凋亡基因和抗凋亡基因表达以及软骨退行性和软骨保护基因的表达在 SF 白细胞中都被激活。因此,在这种单次 LPS 诱导的关节炎模型中,在关节炎急性期浸润关节的白细胞中的炎症反应得到了很好的协调。本研究首次描述了严重关节炎症期间体内 SF 衍生白细胞的基因表达模式,因此该结果扩展了我们对发炎关节早期局部反应中基本炎症机制的认识。

更新日期:2021-09-23
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