5-Aminosalicylic Acid, A Weak Agonist for Aryl Hydrocarbon Receptor That Induces Splenic Regulatory T Cells
5-Aminosalicylic Acid, A Weak Agonist for Aryl Hydrocarbon Receptor That Induces Splenic Regulatory T Cells
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5-氨基水杨酸，一种诱导脾调节 T 细胞的芳基烃受体的弱激动剂
DOI：
10.1159/000520404
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发表时间：
2021
期刊：
影响因子：
3.1
通讯作者：
Kojima Hiroyuki
中科院分区：
文献类型：
--
作者：
Kubota Atsuhito;Terasaki Masaru;Takai Rie;Kobayashi Masaki;Muromoto Ryuta;Kojima Hiroyuki
前言5-氨基水杨酸(5-ASA)是治疗炎症性肠病的关键药物。最近报道，5-ASA通过芳烃受体(AhR)诱导结肠中的CD4+Foxp3+调节性T细胞(Tregs)，AhR是一种配体激活的转录因子，调节炎症。然而，5-ASA作为AhR激动剂在脾中诱导Tregs的作用尚不清楚。方法在本研究中，我们使用AhR介导的反式激活试验和流式细胞术分析来研究这些主题。结果基于DR-EcoScreen细胞的反式激活实验显示，5-AsA在≥30 0μM(1.3 1~1.4 5倍)浓度范围内为弱的AHR激动剂，而典型的AHR激动剂2，3，7，8-四氯二苯并-对二恶英(TCDD)在0.1 nM(2 2.8倍)的浓度下激活AHR。此外，在原代培养实验中，30 0μM5-AsA处理小鼠脾细胞可显著诱导出CD4+CD2 5+Foxp3+Treg细胞(对照组：9.0%vs.5-ASA：12.65%，p<；0.0 5)，而0.1nM TCDD也显示出显著的Tregs诱导(对照组：9.0%vs.TCDD：14.1%，p<；0.0 5)。有趣的是，这种诱导可通过与AhR拮抗剂CH-223191共同处理而被消除。我们的发现可能为5-ASA调节炎症的机制提供有用的见解。
Introduction5-Aminosalicylic acid (5-ASA) is widely used as a key drug in inflammatory bowel disease. It has been recently reported that 5-ASA induces CD4+ Foxp3+ regulatory T cells (Tregs) in the colon via the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates inflammation. However, the role of 5-ASA as an AhR agonist that induces Tregs in the spleen remains unknown.MethodsIn the present study, we investigated these themes using an AhR-mediated transactivation assay and flow cytometry analysis. The experiments were conducted by using DR-EcoScreen cells and C57BL/6 mice.ResultsThe DR-EcoScreen cell-based transactivation assay revealed that 5-ASA acted as a weak AhR agonist at concentrations of≥ 300 μM (1.31–1.45-fold), and that a typical AhR agonist, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), activated AhR at a concentration of 0.1 nM (22.8-fold). In addition, the treatment of mouse splenic cells with 300 μM 5-ASA in a primary culture assay significantly induced CD4+ CD25+ Foxp3+ Tregs (control vs. 5-ASA: 9.0% vs. 12.65%, p< 0.05), while 0.1 nM TCDD also showed significant induction of Tregs (control vs. TCDD: 9.0% vs. 14.1%, p< 0.05). Interestingly, this induction was eliminated by co-treatment with an AhR antagonist, CH-223191.DiscussionThese results suggest that 5-ASA is a weak agonist of AhR and thereby induces Tregs in spleen cells. Our findings may provide useful insights into the mechanism by which 5-ASA regulates inflammation.
影响因子：
5.3
作者：
Dalei Wu;N. Potluri;Youngchang Kim;F. Rastinejad
通讯作者：
Dalei Wu;N. Potluri;Youngchang Kim;F. Rastinejad
影响因子：
12.6
作者：
Dignass, Axel U.;Bokemeyer, Bernd;Veerman, Henri
通讯作者：
Veerman, Henri