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A New Method for Screening Natural Products to Stimulate IFN-γ Production in Jurkat Human T Lymphocytes.
SLAS Discovery: Advancing the Science of Drug Discovery ( IF 2.7 ) Pub Date : 2020-05-22 , DOI: 10.1177/2472555220922475
Yan Ouyang 1, 2 , Xiaoming Zhong 1 , Hongqun Liao 1 , Pengcheng Zhu 2 , Kaiyuan Luo 1, 2, 3 , Huifang Zhu 1, 2
Affiliation  

Interferon-γ (IFN-γ) is a critical cytokine in the defense against viral and bacterial infection. It is mainly produced by natural killer cells and activated T cells. Given its regulatory role in coordinating cellular and humoral immune responses, IFN-γ is considered to be an effective therapeutic agent in the treatment of viral infection. Here we established a fluorescence-based high-content screening model to find small molecules that can stimulate the production of IFN-γ in human Jurkat cells. After a primary screening of 267 natural products, two hits, Astragalus polyphenols and 6-shogaol, were identified to promote the activity of the IFN-γ promoter and subsequently validated by the flow cytometry assay. Obviously, both Astragalus polyphenols and 6-shogaol exhibited potential to induce the transcription and expression of IFN-γ in a dose-dependent manner. These results indicated that our high-content screening model could be a credible and useful platform to contribute to the discovery of novel molecules to promote the expression of IFN-γ and provide leading compounds for the treatment of viral infectious diseases.

中文翻译:

一种筛选天然产物以刺激 Jurkat 人 T 淋巴细胞产生 IFN-γ 的新方法。

干扰素-γ (IFN-γ) 是防御病毒和细菌感染的关键细胞因子。它主要由自然杀伤细胞和活化的T细胞产生。鉴于其在协调细胞和体液免疫反应中的调节作用,IFN-γ被认为是治疗病毒感染的有效治疗剂。在这里,我们建立了一个基于荧光的高内涵筛选模型,以寻找可以刺激人类 Jurkat 细胞产生 IFN-γ 的小分子。在对 267 种天然产物进行初步筛选后,确定了两种命中物,黄芪多酚和 6-姜烯酚,可促进 IFN-γ 启动子的活性,随后通过流式细胞术测定进行验证。明显地,黄芪多酚和 6-姜烯酚均表现出以剂量依赖性方式诱导 IFN-γ 转录和表达的潜力。这些结果表明,我们的高内涵筛选模型可能是一个可靠且有用的平台,有助于发现促进 IFN-γ 表达的新分子,并为治疗病毒感染性疾病提供先导化合物。
更新日期:2020-05-22
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