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高通量筛选 THP-1 衍生报告巨噬细胞中 CEBPD 调节剂化合物，鉴定抗炎 HDAC 和 BET 抑制剂。

High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors.

机构信息

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany.

出版信息

Int J Mol Sci. 2021 Mar 16;22(6):3022. doi: 10.3390/ijms22063022.

DOI:10.3390/ijms22063022
PMID:33809617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8002291/
Abstract

This study aimed to identify alternative anti-inflammatory compounds that modulate the activity of a relevant transcription factor, CCAAT/enhancer binding protein delta (C/EBPδ). C/EBPδ is a master regulator of inflammatory responses in macrophages (Mϕ) and is mainly regulated at the level of gene transcription initiation. To screen for -modulating compounds, we generated a THP-1-derived reporter cell line stably expressing secreted alkaline phosphatase (SEAP) under control of the defined promoter (). A high-throughput screening of LOPAC and ENZO libraries on LPS- and IFN-γ-activated THP-1 reporter Mϕ identified four epigenetically active hits: two bromodomain and extraterminal domain (BET) inhibitors, I-BET151 and Ro 11-1464, as well as two histone deacetylase (HDAC) inhibitors, SAHA and TSA. All four hits markedly and reproducibly upregulated SEAP secretion and mRNA expression, confirming screening assay reliability. Whereas BET inhibitors also upregulated the mRNA expression of the endogenous , HDAC inhibitors completely abolished it. All hits displayed anti-inflammatory activity through the suppression of and gene expression. However, I-BET151 and HDAC inhibitors simultaneously upregulated the mRNA expression of pro-inflammatory . The modulation of CEBPD gene expression shown in this study contributes to our understanding of inflammatory responses in Mϕ and may offer an approach to therapy for inflammation-driven disorders.

摘要

本研究旨在寻找可调节相关转录因子 CCAAT/增强子结合蛋白 δ (C/EBPδ) 活性的抗炎化合物。C/EBPδ 是巨噬细胞 (Mϕ) 中炎症反应的主要调节因子，主要在基因转录起始水平进行调节。为了筛选具有调节作用的化合物，我们生成了一种稳定表达分泌型碱性磷酸酶 (SEAP) 的 THP-1 衍生报告细胞系，该细胞系受定义的启动子 () 的控制。通过对 LPS 和 IFN-γ 激活的 THP-1 报告 Mϕ 进行 LOPAC 和 ENZO 文库的高通量筛选，鉴定出四种具有表观遗传活性的化合物：两种溴结构域和末端结构域 (BET) 抑制剂 I-BET151 和 Ro 11-1464，以及两种组蛋白去乙酰化酶 (HDAC) 抑制剂 SAHA 和 TSA。这四种化合物均显著且可重复地上调 SEAP 分泌和 mRNA 表达，证实了筛选检测的可靠性。虽然 BET 抑制剂也上调了内源性 的 mRNA 表达，但 HDAC 抑制剂完全抑制了它。所有四种化合物均通过抑制 和 基因表达发挥抗炎作用。然而，I-BET151 和 HDAC 抑制剂同时上调了促炎 的 mRNA 表达。本研究中 CEBPD 基因表达的调节有助于我们理解 Mϕ 中的炎症反应，并可能为炎症驱动的疾病提供一种治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd8f/8002291/4d72097b33f9/ijms-22-03022-g006.jpg
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3
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5
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