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自噬与全身型幼年特发性关节炎发生的关系及其相关机制的初步研究
Association between autophagy and systemic juvenile idiopathic arthritis and related mechanism: a preliminary study
目的 通过研究全身型幼年特发性关节炎（sJIA）患儿外周血淋巴细胞中微管相关蛋白轻链3-Ⅱ（LC3-Ⅱ）、髓样细胞分化因子88（MyD88）及T细胞受体信号抑制因子1（STS-1）的表达，探讨自噬在sJIA发生发展中的作用。方法 26例sJIA患儿及26例健康体检的儿童（对照组）纳入研究。采用Western blot检测外周血淋巴细胞中LC3-Ⅱ、STS-1及MyD88蛋白的表达水平，免疫荧光法检测LC3-Ⅱ在淋巴细胞胞浆中的表达，并采用Pearson相关分析法进行各指标间的相关性分析。结果 sJIA组LC3-Ⅱ、STS-1、MyD88表达均较对照组显著增高，差异有统计学意义（P < 0.05）。sJIA组LC3-Ⅱ表达与MyD88表达呈正相关（r=0.478，P < 0.05）；STS-1表达与MyD88表达亦呈正相关（r=0.817，P < 0.01）。结论 sJIA患儿外周血淋巴细胞LC3-Ⅱ高表达，提示sJIA的发生发展与自噬过度表达有关；STS-1可能通过激活某些信号通路诱导自噬的发生；MyD88可能通过Toll样受体信号通路参与自噬的发生。
Objective To study the role of autophagy in the development of systemic juvenile idiopathic arthritis (sJIA) by analyzing the expression of microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ), myeloid differentiation factor 88 (MyD88), and suppressor of T-cell receptor signaling 1 (STS-1) in peripheral blood lymphocytes of children with sJIA. Methods A total of 26 children with sJIA were enrolled as the sJIA group, and 26 healthy children were enrolled as the control group. Western blot was used to measure the protein expression of LC3-Ⅱ, STS-1, and MyD88 in peripheral blood lymphocytes. Immunofluorescence assay was used to measure the expression of LC3-Ⅱ in the cytoplasm of lymphocytes. Pearson correlation analysis was used to assess the correlation between indices. Results Compared with the control group, the sJIA group had significant increases in the expression of LC3-Ⅱ, STS-1, and MyD88 (P < 0.05). In the sJIA group, the expression of LC3-Ⅱ was positively correlated with that of MyD88 (r=0.478, P < 0.05), and the expression of STS-1 was also positively correlated with that of MyD88 (r=0.817, P < 0.05). Conclusions There is high expression of LC3-Ⅱ in peripheral blood lymphocytes of children with sJIA, suggesting that the development of sJIA may be associated with excessive expression of autophagy. STS-1 may induce autophagy by activating some signaling pathways, and MyD88 may participate in autophagy through the Toll-like receptor signaling pathway.
全身型幼年特发性关节炎 / 自噬 / 微管相关蛋白轻链3-Ⅱ / T细胞受体信号抑制因子1 / 髓样细胞分化因子88 / 儿童
Systemic juvenile idiopathic arthritis / Autophagy / Suppressor of T-cell receptor signaling 1 / Microtubule-associated protein 1 light chain 3-Ⅱ / Myeloid differentiation factor 88 / Child
[1] Kahn PJ. Juvenile idiopathic arthritis-what the clinician needs to know[J]. Bull Hosp Jt Dis, 2013, 71(3):194-199.
[2] Dewoolkar M, Cimaz R, Chickermane PR, et al. Course, outcome and complications in children with systemic onset juvenile idiopathic arthritis[J]. Indian J Pediatr, 2017, 84(4):294-298.
[3] 杨圣海.细胞免疫在幼年特发性关节炎致病机制中的研究进展[J].中国社区医师, 2013, 15(2):7-8.
[4] Aksentijevich I, McDermott MF. Lessons from characterization and treatment of the auto-inflammatory syndromes[J]. Curr Opin Rheumatol, 2017, 29(2):187-194.
[5] Zhou XT, Pu ZJ, Liu LX, et al. Inhibition of autophagy enhances adenosine-induced apoptosis in human hepatoblastoma HepG2 cells[J]. Oncol Rep, 2019, 41(2):829-838.
[6] 韩旭,汪威言,张跃,等.自噬在风湿病中的研究进展[J].中华医学杂志, 2018, 98(13):1030-1032.
[7] 杨其彬,周京国.自噬与Toll样受体NOD样受体信号通路相互调控在痛风炎症反应中的作用[J].中华风湿病学杂志, 2015, 19(5):349-351.
[8] 全国儿童风湿病协作组.儿童风湿病诊断及治疗专家共识(一)[J].临床儿科杂志, 2010, 28(10):984-991.
[9] Weindel CG, Richey LJ, Bolland S, et al. B cell autophagy mediates TLR7-dependent autoimmunity and inflammation[J]. Autophagy, 2015, 11(7):1010-1024.
[10] Aoyagi T, Kusakari Y, Xiao CY, et al. Cardiac mTOR protects the heart against ischemia-reperfusion injury[J]. Am J Physiol Am J Physiol Heart Circ Physiol, 2012, 303(1):H75-H85.
[11] 杨淑丽,陈卫昌,孙楹,等.自噬相关基因LC3和Beclin1在大鼠急性坏死性胰腺炎中的表达和意义[J].世界华人消化杂志, 2011, 19(12):1231-1236.
[12] 许珂,蔡永松,鲁超,等.甲氨蝶呤通过诱导自噬促进类风湿关节炎滑膜成纤维细胞凋亡机制的研究[J].中华风湿病学杂志, 2019, 23(2):106-109.
[13] 李永柏,梁芳芳.自身炎症性疾病与自身免疫性疾病[J].中华实用儿科临床杂志, 2013, 28(9):641-643.
[14] Yokota S, Kikuchi M, Nozawa T, et al. Pathogenesis of systemic inflammatory diseases in childhood:"Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease, systemic onset juvenile idiopathic arthritis, and cryopyrinassociated periodic fever syndrome"[J]. Mod Rheumatol, 2015, 25(1):1-10.
[15] Avbelj M, Horvat S, Jerala R. The role of intermediary domain of MyD88 in cell activation and therapeutic inhibition of TLRs[J]. J Immunol, 2011, 187(5):2394-2404.
[16] Loiarro M, Capolunghi F, Fantò N, et al. Pivotal advance:inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound[J]. J Leukoc Biol, 2007, 82(4):801-810.
[17] 陈姣姣,唐雪梅.预测幼年特发性关节炎预后不良的生物学标志物研究进展[J].国际免疫学杂志, 2019, 42(2):224-228.
[18] Holzinger D, Foell D, Kessel C. The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases[J]. Mol Cell Pediatr, 2018, 5(1):7.
[19] Liu M, Guo Q, Wu C, et al. Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients[J]. Cell Mol Immunol, 2019, 16(4):367-379.
[20] Lee ST, Feng M, Wei Y, et al. Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis[J]. Proc Natl Acad Sci U S A, 2013, 110(27):11121-11126.
[21] Dong G, You M, Fan H, et al. STS-1 promotes IFN-α induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells[J]. Eur J Immunol, 2015, 45(8):2377-2388.
