Abstract：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.
ZHAO Jie,ZHAO Xue,DOU Zhi-Yan et al. Association between autophagy and systemic juvenile idiopathic arthritis and related mechanism: a preliminary study[J]. CJCP, 2019, 21(10): 966-971.
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.
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.
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.
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.
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.
