受体酪氨酸激酶Axl在自身抗体诱导关节炎发病中的作用

摘要
图/表
参考文献
相关文章 (12)

全文: PDF (1656 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要
［摘要］目的: 研究受体酪氨酸激酶Axl在自身抗体诱导关节炎发病中的作用。方法: 分别向Axl基因敲除小鼠和同窝野生型小鼠腹腔内注射K/BxN血清，诱导其发生关节炎。运用临床评分和测量小鼠踝关节直径，分析两组小鼠关节炎发病严重程度。通过HE染色和番红O固绿染色观察踝关节组织病理变化；采用ELISA法检测关节组织研磨液中肿瘤坏死因子α（TNFα）和白细胞介素（IL6）的蛋白水平；采用实时定量PCR技术检测关节组织和外周血白细胞中TNFα和IL6的mRNA水平。结果：与同窝野生型小鼠相比，Axl基因敲除小鼠关节炎发病的严重程度显著增加，踝关节组织呈现更为显著的滑膜增生以及骨与软骨的侵蚀性破坏，踝关节组织中TNFα和IL6的蛋白和mRNA水平显著增加，外周血白细胞中TNFα和IL6在mRNA水平上亦增加。结论：受体酪氨酸激酶Axl在自身抗体诱导的关节炎发病中起免疫抑制作用。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章

关键词 ：关节炎, 类风湿, 受体酪氨酸激酶, 自身抗体

Abstract：［Abstract］Objective： To explore the role of receptor tyrosine kinase Axl in the autoantibodyinduced arthritis. Methods：Both the Axldeficient mice and their littermate control wildtype mice were transferred with K/BxN serum to induce arthritis by intraperitoneal injection. Then the degree of arthritis were assessed with ankle thickness and clinical scores. At the same time, HE staining and safraninOfast green staining were carried out to detect the histological changes. In addition, ELISA was performed to determine the protein level of tumor necrosis factorα (TNFα) and interleukin 6 (IL6) in joint tissues. Furthermore, the mRNA levels of TNFα and IL6 in joint tissues and leukocytes were detected by QPCR. Results：Axl deficiency aggravated the severity of arthritis and synovial inflammation. The cartilage damage and bone erosion were severer than the control. Importantly, the levels of TNFα and IL6 were also increased significantly in joint tissues and leukocytes. Conclusion： Axl plays a protective role in autoantibodyinduced arthritis.

收稿日期: 2016-03-10

基金资助:

苏州大学“211工程”建设经费资助项目（14121903）；国家自然科学基金资助项目（K121123312、81301534）；苏州市科技计划项目（SYS201314）

通讯作者: 武艺（通讯作者），医学博士，E-mail：wuy@suda.edu.cn

作者简介: 高亮（1989—），男，硕士研究生；

引用本文:

高亮，阳艾珍，武艺. 受体酪氨酸激酶Axl在自身抗体诱导关节炎发病中的作用[J]. 江苏大学学报:医学版, 2016, 26(04): 307-310,315. GAO Liang, YANG Ai-zhen, WU Yi. Role of Axl in the autoantibodyinduced arthritis. Journal of Jiangsu University(Medicine Edition), 2016, 26(04): 307-310,315.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2016/V26/I04/307

［1］Kouskoff V, Korganow AS, Duchatelle V, et al. Organspecific disease provoked by systemic autoimmunity \[J\]. Cell, 1996, 87(5): 811-822.
［2］Holmdahl R, Malmstrm V, Burkhardt H. Autoimmune priming, tissue attack and chronic inflammationthe three stages of rheumatoid arthritis \[J\]. Eur J Immunol, 2014, 44(6): 1593-1599.
［3］Ji H, Ohmura K, Mahmood U, et al. Arthritis critically dependent on innate immune system players \[J\]. Immunity, 2002, 16(2): 157-168.
［4］Ditzel HJ. The K/BxN mouse: a model of human inflammatory arthritis\[J\]. Trends Mol Med, 2004, 10(1): 40-45.
［5］Rothlin CV, Ghosh S, Zuniga EI, et al. TAM receptors are pleiotropic inhibitors of the innate immune response \[J\]. Cell, 2007, 131(6): 1124-1136.
［6］Bassyouni IH, ElWakd MM, Azab NA, et al. Diminished soluble levels of growth arrest specific protein 6 and tyrosine kinase receptor Axl in patients with rheumatoid arthritis \[J\]. Int J Rheum Dis, 2014, 1111/1756-185X
［7］Monach PA, Mathis D, Benoist C. The K/BxN arthritis model \[J\]. Curr Protoc Immunol, 2008, Chapter 15:Unit 15.22. doi: 10.1002/0471142735.im1522s81.
［8］Kim ND, Chou RC, Seung E, et al. A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis \[J\]. J Exp Med, 2006, 203(4): 829-835.
［9］Rose S, Waters EA, Haney CR, et al. Highresolution magnetic resonance imaging of ankle joints in murine arthritis discriminates inflammation and bone destruction in a quantifiable manner \[J\]. Arthritis Rheum, 2013, 65(9): 2279-2289.
［10］Garcia S, Forteza J, LopezOtin C, et al. Matrix metalloproteinase8 deficiency increases joint inflammation and bone erosion in the K/BxN serumtransfer arthritis model \[J\]. Arthritis Res Ther, 2010, 12(6): R224.
［11］D′Arcangelo D, Gaetano C, Capogrossi MC. Acidification prevents endothelial cell apoptosis by Axl activation \[J\]. Circ Res, 2002, 91(7): e4-12.
［12］Fridell YW, Jin Y, Quilliam LA, et al. Differential activation of the Ras/extracellularsignalregulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase \[J\]. Mol Cell Biol, 1996, 16(1): 135-145.
［13］Hafizi S, Ibraimi F, Dahlback B. C1TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration \[J\]. FASEB J, 2005, 19(8): 971-973.
［14］Bellosta P, Costa M, Lin DA, et al. The receptor tyrosine kinase ARK mediates cell aggregation by homophilic binding \[J\]. Mol Cell Biol, 1995, 15(2): 614-625.
［15］Liu H, Pope RM. The role of apoptosis in rheumatoid arthritis \[J\]. Curr Opin Pharmacol, 2003, 3(3): 317-322.
［16］Rothlin CV, Lemke G. TAM receptor signaling and autoimmune disease \[J\]. Curr Opin Immunol, 2010, 22(6): 740-746.
［17］Lemke G, Rothlin CV. Immunobiology of the TAM receptors \[J\]. Nat Rev Immunol, 2008, 8(5): 327-336.

［18］Pruessmeyer J, Hess FM, Alert H, et al. Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space \[J\]. Blood, 2014, 123(26): 4077-4088.
［19］Alciato F, Sainaghi PP, Sola D, et al. TNFα, IL6, and IL1 expression is inhibited by GAS6 in monocytes/macrophages \[J\]. J Leukoc Biol, 2010, 87(5): 869-875.
［20］Ji H, Pettit A, Ohmura K, et al. Critical roles for interleukin 1 and tumor necrosis factor α in antibodyinduced arthritis \[J\]. J Exp Med, 2002, 196(1): 77-85.
［21］Blom AB, Radstake TR, Holthuysen AE, et al. Increased expression of Fcγ receptors Ⅱ and Ⅲ on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase \[J\]. Arthritis Rheum, 2003, 48(4): 1002-1014.
［22］Mancardi DA, Jonsson F, Iannascoli B, et al. Cutting Edge: The murine highaffinity IgG receptor FcγRⅣ is sufficient for autoantibodyinduced arthritis \[J\]. J Immunol, 2011, 186(4): 1899-1903.
［23］AbdollahiRoodsaz S, Koenders MI, Walgreen B, et al. Tolllike receptor 2 controls acute immune complexdriven arthritis in mice by regulating the inhibitory Fcγ receptor ⅡB \[J\]. Arthritis Rheum, 2013, 65(10): 2583-2593.
［24］Godau J, Heller T, Hawlisch H, et al. C5a initiates the inflammatory cascade in immune complex peritonitis \[J\]. J Immunol, 2004, 173(5): 3437-3445.