Department of Medical Immunology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran.
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Endocr Metab Immune Disord Drug Targets. 2020;20(6):878-886. doi: 10.2174/1871530319666190729112246.
Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. The most common disease phenotype is Relapsing-Remitting MS (RRMS). Beta interferons are the first line of RRMS patients' treatment. Interferon-inducible protein 16 (IFI16) as a DNA sensing molecule and its downstream complex stimulator of interferon genes (STING) play a critical role in the activation of type I interferons. Hence we aimed to evaluate the expression rate of IFI16 and STING in RRMS patients' blood under a different type of IFNβ treatment.
In the present study, 99 individuals participated. The participants were divided into 4 groups: 28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with IFNβ-1a (B1a), 21 RRMS patients treated with IFNβ-1b (B1b). The EDTA-treated blood samples were taken and transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted into cDNA. To evaluate the expression of IFI16 and STING, the Real-Time PCR method using SYBR Green/ROX qPCR master mix was performed done. The level of genes expression was measured using 2-ΔΔCt method. The obtained data were analyzed using SPSS v22 software.
Comparison of the IFI and STING mRNA expression in blood samples in association with gender and age showed no significant differences (p>0.05). Also, the evaluation of IFI16 mRNA level revealed that the IFI16 genes' expressions were remarkably higher in the new case group compared to the control group, however, STING expression did not show any significant difference. The mRNA levels of IFI16 and STING in IFNβ-treated groups were significantly lower than the new case group (p<0.001). Also, the genes' expressions in both the IFNβ-treated groups were significantly lower compared to the control group (p<0.001). In the assessment of the correlation of IFI16 and STING expressions with age and sex in different research groups, no statistically significant differences were seen (p>0.05).
Perhaps the IFNβ therapy decreases the IFI16 and STING expression in a STINGdependent pathway as a negative feedback mechanism for regulation of the immune system and suppression of pro-inflammatory cytokines production. The important role of DNA sensing molecules and STING-dependent pathway in MS gives a new insight into future treatment based on STING-direct therapies.
多发性硬化症（MS）是一种中枢神经系统的慢性神经退行性疾病。最常见的疾病表型是复发缓解型多发性硬化症（RRMS）。β干扰素是 RRMS 患者的一线治疗药物。干扰素诱导蛋白 16（IFI16）作为一种 DNA 感应分子及其下游干扰素基因刺激物（STING）复合物在 I 型干扰素的激活中起着关键作用。因此，我们旨在评估在不同类型 IFNβ 治疗下 RRMS 患者血液中 IFI16 和 STING 的表达率。
本研究共纳入 99 名参与者。参与者分为 4 组：28 名对照组、25 名新发 RRMS 患者、25 名接受 IFNβ-1a（B1a）治疗的 RRMS 患者和 21 名接受 IFNβ-1b（B1b）治疗的 RRMS 患者。采集 EDTA 处理的血液样本，并在标准条件下转移至沙赫里库尔德大学医学科学细胞和分子研究中心，提取 RNA 并转化为 cDNA。使用 SYBR Green/ROX qPCR 主混合物进行实时 PCR 方法以评估 IFI16 和 STING 的表达。使用 2-ΔΔCt 方法测量基因表达水平。使用 SPSS v22 软件分析获得的数据。
比较血液样本中与性别和年龄相关的 IFI 和 STING mRNA 表达，结果无显著差异（p>0.05）。此外，IFI16 mRNA 水平的评估表明，新病例组 IFI16 基因的表达明显高于对照组，而 STING 表达无显著差异。IFNβ 治疗组的 IFI16 和 STING mRNA 水平明显低于新病例组（p<0.001）。此外，两组 IFNβ 治疗组的基因表达均明显低于对照组（p<0.001）。在不同研究组中评估 IFI16 和 STING 表达与年龄和性别之间的相关性时，未见统计学差异（p>0.05）。
也许 IFNβ 治疗通过 STING 依赖性途径降低 IFI16 和 STING 的表达，作为免疫系统调节和抑制促炎细胞因子产生的负反馈机制。DNA 感应分子和 STING 依赖性途径在 MS 中的重要作用为基于 STING 直接治疗的未来治疗提供了新的见解。
