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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 >Role of differential expression of interferon receptor isoforms on the response of multiple sclerosis patients to therapy with interferon beta.
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Role of differential expression of interferon receptor isoforms on the response of multiple sclerosis patients to therapy with interferon beta.

机译:干扰素受体同工型的差异表达在多发性硬化症患者对β干扰素治疗的反应中的作用。

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摘要

The cytokine interferon (IFN)-beta is successfully used in the treatment of multiple sclerosis. However, some patients fail to respond to therapy, probably due to different biological patterns that are of importance in influencing clinical response. A common mechanism involved in the modulation of responsiveness to cytokine is represented by regulation of their receptor expression through autocrine-ligand-mediated loops. Mechanistically, IFN-beta exerts its biological effects through interaction with the IFN-alpha/-beta-receptor (IFNAR), which then activates several transcription factors. IFNAR is composed of 2 chains, IFNAR-1 and IFNAR-2, which associate with IFN-beta to form a ternary complex. The major ligand-binding subunit is IFNAR-2 and it exists in 3 mRNA splice variants, resulting in 2 transmembrane (IFNAR-2b and IFNAR-2c) isoforms and a soluble (IFNAR-2a) one. On the contrary, from normal cells only one IFNAR-1 isoform, with transcriptional capacity, was identified. In the past decades, considerable information has accumulated pertaining to the downregulation of the IFNAR complex in IFN-treated patients, but only a few studies have investigated the molecular events involved in this phenomenon. The intent of the present review is to place this receptor downregulation in the context of IFN-beta therapy and of its clinical and biological outcomes in IFN-beta-treated patients.
机译:细胞因子干扰素(IFN)-β已成功用于治疗多发性硬化症。但是,某些患者对治疗无效,可能是由于不同的生物学模式对影响临床反应具有重要意义。通过自分泌配体介导的环调节其受体表达来代表参与调节对细胞因子的反应性的共同机制。从机制上讲,IFN-β通过与IFN-α/β-受体(IFNAR)相互作用发挥其生物学作用,然后激活几个转录因子。 IFNAR由两条链IFNAR-1和IFNAR-2组成,它们与IFN-β结合形成三元复合物。主要的配体结合亚基是IFNAR-2,它以3种mRNA剪接变体形式存在,产生2种跨膜(IFNAR-2b和IFNAR-2c)同工型和一种可溶性(IFNAR-2a)同工型。相反,从正常细胞中仅鉴定出一种具有转录能力的IFNAR-1同工型。在过去的几十年中,已经积累了有关在IFN治疗的患者中IFNAR复合物下调的大量信息,但是只有少数研究调查了与该现象有关的分子事件。本综述旨在将这种受体下调置于IFN-β治疗及其在IFN-β治疗的患者中的临床和生物学结果的背景下。

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