PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis.
PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis.
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DOI：
10.1186/ar3829
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发表时间：
2012-05-02
影响因子：
4.9
通讯作者：
Mowen KA
中科院分区：
文献类型：
--
作者：
Rohrbach AS;Hemmers S;Arandjelovic S;Corr M;Mowen KA
小鼠和人类全基因组关联研究均表明肽基精氨酸脱亚胺酶（PAD 4）是类风湿关节炎（RA）的易感基因。此外，RA患者通常具有识别PAD 4或/或瓜氨酸化肽的自身抗体。本研究旨在评估PAD 4在关节炎效应期的作用。用K/BxN血清注射PAD 4敲除（KO）和野生型（WT）C57 BL/6 J小鼠以诱导疾病。通过测量爪和踝肿胀以及疾病的临床指数来监测疾病的进展，并且通过对从注射K/BxN血清的WT和PAD 4 KO小鼠收集的爪的临床进展进行索引来评估发病机制。通过观察中性粒细胞胞外陷阱（NET）和组蛋白瓜氨酸酶的免疫组织学分析确定PAD 4活性。如组蛋白瓜氨酸酶和NET形成所证明的，在WT动物的发炎滑膜中容易检测到PAD 4活性，但在PAD 4缺陷动物的发炎滑膜中检测不到。然而，PAD 4 WT和KO动物发展出严重程度和动力学相当的K/BxN血清转移疾病，在临床评分、肿胀、关节侵蚀或关节侵入方面没有观察到统计学显著差异。PAD 4 WT和KO小鼠在关节炎的K/BxN血清转移模型中以相似的严重程度和动力学发展疾病，表明PAD 4在该疾病的效应期模型中被抑制。
Both murine and human genome-wide association studies have implicated peptidyl arginine deiminase (PAD4) as a susceptibility gene in rheumatoid arthritis (RA). In addition, patients with RA commonly have autoantibodies which recognize PAD4 or and/or citrullinated peptides. This study aims to evaluate the role of PAD4 in the effector phase of arthritis. PAD4 knock out (KO) and wild type (WT) C57BL/6J mice were injected with K/BxN sera to induce disease. Progression of disease was monitored by measuring paw and ankle swelling and clinical indexes of disease, and pathogenesis was assessed by indexing of clinical progression on paws collected from WT and PAD4 KO mice injected with K/BxN serum. PAD4 activity was determined by visualization of neutrophil extracellular traps (NETs) and immunohistological analysis of histone citrullination. PAD4 activity is readily detectable in the inflamed synovium of WT but not PAD4 deficient animals, as demonstrated by histone citrullination and NET formation. However, PAD4 WT and KO animals develop K/BxN serum transfer disease with comparable severity and kinetics, with no statistically significant differences noted in clinical scores, swelling, joint erosion or joint invasion. PAD4 WT and KO mice develop disease in the K/BxN serum transfer model of arthritis with similar severity and kinetics, indicating that PAD4 is dispensable in this effector phase model of disease.
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影响因子：
3.7
作者：
Hemmers S;Teijaro JR;Arandjelovic S;Mowen KA
通讯作者：
Mowen KA
DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.9
作者：
Knuckley, Bryan;Causey, Corey P.;Jones, Justin E.;Bhatia, Monica;Dreyton, Christina J.;Osborne, Tanesha C.;Takahara, Hidenari;Thompson, Paul R.
通讯作者：
Thompson, Paul R.
影响因子：
56.9
作者：
Lee, DM;Friend, DS;Brenner, MB
通讯作者：
Brenner, MB