Imperatorin inhibits LPS-induced bone marrow-derived macrophages activation by decreased NF-κB p65 phosphorylation.

IF 2.9 4区医学 Q3 IMMUNOLOGY

Immunopharmacology and Immunotoxicology Pub Date : 2023-10-01 Epub Date: 2023-04-11 DOI:10.1080/08923973.2023.2196603

Yuan Jiang, Hui Fang, Siqi Lin, Yunyun Chen, Yuanzheng Fu, Yifan Tu, Qiang Li, Zhaoyuan Hui

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引用次数: 0

Abstract

Background: Imperatorin (IMP) is a secondary metabolite of plants and is the most abundant in Angelica dahurica. Previous studies showed that IMP exhibited anti-inflammatory activity in RAW264.7 cell line. Here, we aim to investigate the roles and mechanisms of IMP in bone marrow-derived macrophages (BMDMs), in view of the difference between primary macrophages and cell lines.

Methods: BMDMs were stimulated with LPS for the inflammation model. Flow cytometry was performed with BMDMs treated with different doses of IMP (0-20mg/L) within staining Annexin V-APC for 5 min. The cytokines and inflammatory mediators were detected by RT-PCR or ELISA. RNA-seq was performed in IMP-treated BMDMs or control, stimulated with LPS for 6h. Western blotting is carried out to determine the phosphorylation of p65, ERK1/2, JNK1, p38, and Akt.

Results: Our results showed that IMP inhibited IL-12p40, IL-6, TNF-α and IL-1β in LPS-stimulated BMDMs. RNA-seq analysis suggested that IMP inhibits Toll-like receptor signaling pathway (KEGG), TNF signaling pathway (KEGG), NF-κB signaling pathway (KEGG), Inflammatory Response (GO). In addition, IMP inhibited myd88, tpl2, cxcl1, ptgs2(COX-2) expression in mRNA level. Finally, we found decreased phosphorylation of NF-κB p65 in IMP-treated BMDMs, after stimulated with LPS.

Conclusion: IMP inhibits IL-12p40, IL-6, TNF-α, and IL-1β expression in LPS-stimulated BMDMs. IMP inhibits macrophage activation, which maybe resulted in decreased phosphorylation of NF-κB p65. Furthermore, IMP may protect against the progress of inflammatory-related diseases.

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Imperatorin通过降低NF-κB p65磷酸化作用抑制LPS诱导的骨髓源性巨噬细胞活化。

背景：Imperatorin（IMP）是植物的次生代谢产物，在白芷中含量最高。先前的研究表明IMP在RAW264.7细胞系中表现出抗炎活性。鉴于原代巨噬细胞和细胞系之间的差异，我们旨在研究IMP在骨髓源性巨噬细胞（BMDMs）中的作用和机制。方法：用LPS刺激骨髓基质干细胞建立炎症模型。用不同剂量IMP（0-20mg/L）处理的BMDM进行流式细胞术，对膜联蛋白V-APC染色5 min。RT-PCR或ELISA检测细胞因子和炎症介质。在用LPS刺激6小时的IMP处理的BMDMs或对照中进行RNA-seq。Western印迹法检测p65、ERK1/2、JNK1、p38和Akt的磷酸化。结果：IMP抑制LPS刺激的BMDMs中的IL-12p40、IL-6、TNF-α和IL-1β。RNA-seq分析表明，IMP抑制Toll样受体信号通路（KEGG）、TNF信号通路（KEGG），NF-κB信号通路（KEGG）和炎症反应（GO）。此外，IMP在mRNA水平上抑制myd88、tpl2、cxcl1、ptgs2（COX-2）的表达。最后，我们发现LPS刺激后，IMP处理的BMDMs中NF-κB p65的磷酸化降低。结论：IMP抑制LPS刺激的BMDMss中IL-12p40、IL-6、TNF-α和IL-1β的表达。IMP抑制巨噬细胞活化，这可能导致NF-κB p65的磷酸化降低。此外，IMP可以预防炎症相关疾病的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).