Department of Medical Research, Show Chwan Memorial Hospital in Chang Bing, Changhua 505, Taiwan.
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
J Infect. 2014 Oct;69(4):366-74. doi: 10.1016/j.jinf.2014.05.013. Epub 2014 Jun 5.
Suppressors of cytokine signalling (SOCS) proteins regulate cytokine responses and control immune balance. The objective of our study was to determine whether the expression of SOCS1 and its potential regulatory microRNAs (miRNAs) in leukocytes is correlated to the development of dengue haemorrhagic fever (DHF).
We performed a case-control study to investigate the SOCS1 and miRNA expression in leukocytes for patients with DF and DHF in a DENV-2 outbreak that occurred in Taiwan between 2002 and 2003. We performed reverse transcription polymerase chain reaction to evaluate the expression of SOCS1 and its regulatory miRNAs in mononuclear leukocytes obtained from patients with or without DHF. The reciprocal relationship between SOCS1 and miR-150 expression was validated in DENV-2-infected peripheral mononuclear cells (PBMCs).
SOCS1 expression and lower IFN-γ level were significantly reduced in DHF patients, but not in patients with DF. Elevated SOCS1 and reduced miR-150 levels were detected 24 h after DENV-2 infection in PBMCs. Transfection of a miR-150 mimic into CD14(+) cells infected with DENV-2 suppressed the induction of SOCS1 expression in a dose-dependent manner.
We demonstrate for the first time that augmented miR-150 expression with depressed SOCS1 expression in CD14(+) cells are associated with the pathogenesis of DHF.
细胞因子信号转导抑制蛋白(SOCS)家族可调节细胞因子的反应,控制免疫平衡。本研究旨在探讨白细胞中 SOCS1 及其潜在调控 microRNA(miRNA)的表达与登革出血热(DHF)的发生发展是否相关。
我们开展了一项病例对照研究,对 2002-2003 年台湾登革热 2 型病毒爆发期间,登革热(DF)和登革出血热(DHF)患者外周血单个核细胞(PBMC)中 SOCS1 及其调控 miRNA 的表达进行了评估。采用逆转录聚合酶链反应检测有无 DHF 的患者单核细胞中 SOCS1 的表达。在 DENV-2 感染的外周血单核细胞(PBMC)中验证 SOCS1 与 miR-150 表达的相互关系。
与 DF 患者相比,DHF 患者 SOCS1 表达降低,IFN-γ 水平显著降低,但未在 DF 患者中发现。DENV-2 感染后 24 h,PBMC 中 SOCS1 和 miR-150 水平升高。用 miR-150 模拟物转染感染 DENV-2 的 CD14(+)细胞,可呈剂量依赖性抑制 SOCS1 表达的诱导。
本研究首次证实,CD14(+)细胞中 miR-150 表达上调伴 SOCS1 表达下调与 DHF 的发病机制有关。