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Increased IL-6 Levels and the Upregulation of Iron Regulatory Biomarkers Contribute to the Progression of Japanese Encephalitis Virus Infection’s Pathogenesis
NeuroMolecular Medicine ( IF 3.5 ) Pub Date : 2023-10-31 , DOI: 10.1007/s12017-023-08762-1
Anjali Singh 1 , Sneha Ghildiyal 2 , Prabhaker Mishra 3 , Gajendra Singh 1 , Himanshu Dandu 4 , Alok Kumar 1
Affiliation  

Integrated analysis of iron regulatory biomarkers and inflammatory response could be an important strategy for Japanese encephalitis viral (JEV) infection disease management. In the present study, the inflammatory response was assessed by measuring serum Interleukin-6 (IL-6) levels using ELISA, and the transcription levels of iron homeostasis regulators were analyzed via RT-PCR. Furthermore, inter-individual variation in the transferrin gene was analyzed by PCR–RFLP and their association with clinical symptoms, susceptibility, severity, and outcomes was assessed through binary logistic regression and classification and regression tree (CART) analysis. Our findings revealed elevated levels of IL-6 in serum as well as increased expression of hepcidin (HAMP), transferrin (TF), and transferrin receptor-1 (TFR1) mRNA in JEV infection cases. Moreover, we found a genetic variation in TF (rs4481157) associated with clinical symptoms of meningoencephalitis. CART analysis indicates that individuals with the wild-type TF genotype are more susceptible to moderate JEV infection, while those with the homozygous type are in the high-risk group to develop a severe JEV condition. In summary, the study highlights that JEV infection induces alteration in both IL-6 levels and iron regulatory processes, which play pivotal roles in the development of JEV disease pathologies.



中文翻译:

IL-6 水平升高和铁调节生物标志物上调有助于日本脑炎病毒感染发病机制的进展

铁调节生物标志物和炎症反应的综合分析可能是日本脑炎病毒(JEV)感染疾病管理的重要策略。在本研究中,通过使用 ELISA 测量血清白介素 6 (IL-6) 水平来评估炎症反应,并通过 RT-PCR 分析铁稳态调节因子的转录水平。此外,通过 PCR-RFLP 分析转铁蛋白基因的个体间变异,并通过二元 Logistic 回归和分类回归树 (CART) 分析评估其与临床症状、易感性、严重程度和结果的关联。我们的研究结果显示,在乙脑病毒感染病例中,血清中 IL-6 水平升高,铁调素 (HAMP)、转铁蛋白 (TF) 和转铁蛋白受体 1 (TFR1) mRNA 表达增加。此外,我们发现 TF (rs4481157) 的遗传变异与脑膜脑炎的临床症状相关。CART分析表明,具有野生型TF基因型的个体更容易感染中度JEV,而具有纯合型的个体则属于发展为严重JEV的高危人群。总之,该研究强调,JEV 感染会引起 IL-6 水平和铁调节过程的改变,这在 JEV 疾病病理学的发展中发挥着关键作用。

更新日期:2023-11-02
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