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首页> 外文期刊>Journal of interferon and cytokine research: The official journal of the International Society for Interferon and Cytokine Research >IFN-beta1b induces transient and variable gene expression in relapsing-remitting multiple sclerosis patients independent of neutralizing antibodies or changes in IFN receptor RNA expression.
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IFN-beta1b induces transient and variable gene expression in relapsing-remitting multiple sclerosis patients independent of neutralizing antibodies or changes in IFN receptor RNA expression.

机译:IFN-beta1b在复发缓解型多发性硬化症患者中诱导瞬时和可变基因表达,而独立于中和抗体或IFN受体RNA表达的变化。

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摘要

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Interferon-beta (IFN-beta) therapy for MS is hypothesized to cause short-term and long-term changes in gene expression that shift the inflammation from Th1 to Th2. In vivo gene induction to define kinetics of response to IFN-beta therapy in a large cohort of MS patients is described. Differential gene expression in peripheral blood mononuclear cells (PBMCs) obtained from relapsing-remitting MS patients (RRMS) was assessed using high content microarrays. Rapid onset of gene expression appeared within 4 h of subcutaneous IFN-beta administration, returning to baseline levels at 42 h in clinically stable RRMS. IFN-beta therapy in vivo rapidly but transiently induced strong upregulation of genes mediating immune modulation, IFN signaling, and antiviral responses. RT-PCR showed significant patient-to-patient variation in the magnitude of expression of multiple genes, especially for IFN-beta-inducible genes, such as MxA, IRF7, and CCL8, a Th1 product. Variation among patients in IFN-beta-induced RNA transcription was not explained by neutralizing antibodies or IFN receptor expression. Surprisingly, genes regulated in vivo by IFN-beta therapy do not support a simple Th1 to Th2 shift. A complex interplay between both proinflammatory and anti-inflammatory immune regulatory genes is likely to act in concert in the treatment of RRMS.
机译:多发性硬化症(MS)是中枢神经系统(CNS)的炎性疾病。据推测,MS的干扰素-β(IFN-β)治疗可引起基因表达的短期和长期变化,从而使炎症从Th1转变为Th2。描述了体内基因诱导,以定义大量MS患者对IFN-β治疗的反应动力学。使用高含量微阵列芯片评估从复发缓解型MS患者(RRMS)获得的外周血单核细胞(PBMC)中的差异基因表达。皮下注射IFN-β后4小时内基因表达迅速出现,在临床稳定的RRMS中于42小时恢复到基线水平。体内的IFN-β治疗迅速但短暂地诱导介导免疫调节,IFN信号传导和抗病毒反应的基因强烈上调。 RT-PCR显示多种基因表达量在患者之间存在显着差异,尤其是对于IFN-β诱导基因,例如Thx产物MxA,IRF7和CCL8。中和抗体或IFN受体的表达不能解释IFN-β诱导的RNA转录的患者差异。出人意料的是,在体内受IFN-β治疗调节的基因不支持从Th1到Th2的简单转变。促炎和抗炎免疫调节基因之间的复杂相互作用很可能在RRMS的治疗中协同作用。

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