Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box 14155-6446, Tehran, Iran.
Department of Immunology, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Immunol Res. 2019 Feb;67(1):108-115. doi: 10.1007/s12026-018-9042-3.
The present research aims to study the effects of guluronic acid (G2013) on gene expression levels of the T-bet, GATA3, RORγt, AHR, and FOXP3 transcription factors and on gene expression of their related cytokines following oral administration of this drug in ankylosing spondylitis (AS) patients. In this trial (clinical trial identifier: IRCT2016091813739N4), 14 AS patients and 12 age- and sex-matched healthy individuals were enrolled. The level of transcription factors' gene expression and expression of their related cytokines were measured by quantitative real-time PCR, before and 3 months after G2013 therapy. Our data indicated that the gene expression levels of the T-bet and IFN-γ were not significantly reduced during 12 weeks of treatment with G2013 (p > 0.05). The findings showed that the gene expression levels of the GATA3 and IL-4 increased significantly during 12 weeks of treatment with G2013 (p < 0.05). In addition, gene expression levels of the RORγt, IL-17, AHR, and IL-22 decreased significantly during the 12-week treatment with G2013 (p < 0.05). Moreover, the gene expression level of the FOXP3 increased significantly during 12 weeks of treatment with G2013, but the gene expression level of IL-10 did not increase significantly (p < 0.05, p > 0.05, respectively). The present study showed that oral intake of G2013 was able to modify the severity of articular and inflammatory symptoms of AS through reducing the gene expression levels of the RORγt, IL-17, AHR, and IL-22 and increasing the gene expression levels of the GATA3, IL-4, and FOXP3.
本研究旨在探讨口服 G2013 对强直性脊柱炎（AS）患者 T 细胞转录因子（T-bet）、GATA3、RORγt、AHR 和 FOXP3 及其相关细胞因子基因表达水平的影响。在这项试验（临床试验标识符：IRCT2016091813739N4）中，纳入了 14 名 AS 患者和 12 名年龄和性别匹配的健康对照者。在 G2013 治疗前和治疗 3 个月后，通过实时定量 PCR 测量了转录因子基因表达水平及其相关细胞因子的表达。我们的数据表明，在 G2013 治疗 12 周内，T-bet 和 IFN-γ 的基因表达水平没有显著降低（p>0.05）。结果表明，在 G2013 治疗 12 周内，GATA3 和 IL-4 的基因表达水平显著增加（p<0.05）。此外，在 G2013 治疗 12 周内，RORγt、IL-17、AHR 和 IL-22 的基因表达水平显著降低（p<0.05）。此外，在 G2013 治疗 12 周内，FOXP3 的基因表达水平显著增加，但 IL-10 的基因表达水平没有显著增加（p<0.05，p>0.05）。本研究表明，口服 G2013 能够通过降低 RORγt、IL-17、AHR 和 IL-22 的基因表达水平，增加 GATA3、IL-4 和 FOXP3 的基因表达水平，从而改善 AS 的关节和炎症症状的严重程度。
