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()-萝卜硫素对脂多糖激活的小鼠免疫细胞的免疫调节作用:分子信号通路及组蛋白标记的表观遗传变化

Immunomodulatory Effects of ()-Sulforaphane on LPS-Activated Murine Immune Cells: Molecular Signaling Pathways and Epigenetic Changes in Histone Markers.

作者信息

Alcarranza Manuel, Villegas Isabel, Muñoz-García Rocío, Recio Rocío, Fernández Inmaculada, Alarcón-de-la-Lastra Catalina

机构信息

Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain.

Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.

出版信息

Pharmaceuticals (Basel). 2022 Aug 4;15(8):966. doi: 10.3390/ph15080966.

DOI:10.3390/ph15080966
PMID:36015113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9414446/
Abstract

The aim of this study was to explore the immunomodulatory effects of the natural enantiomer ()-Sulforaphane (SFN) and the possible signaling pathways involved in an ex vivo model of LPS-stimulated murine peritoneal macrophages. Furthermore, we studied the epigenetic changes induced by ()-SFN as well as the post-translational modifications of histone H3 (H3K9me3 and H3K18ac) in relation to the production of cytokines in murine splenocytes after LPS stimulation. ()-SFN was able to modulate the inflammatory response and oxidative stress induced by LPS stimulation in murine peritoneal macrophages through the inhibition of reactive oxygen species (ROS), nitric oxide (NO) and cytokine (IL-1β, IL-6, IL-17, IL-18 and TNF-α) production by down-regulating the expression of pro-inflammatory enzymes (iNOS, COX-2 and mPGES-1). We also found that activation of the Nrf-2/HO-1 axis and inhibition of the JAK2/STAT-3, MAPK, canonical and non-canonical inflammasome signaling pathways could have been responsible for the immunomodulatory effects of ()-SFN. Furthermore, ()-SFN modulated epigenetic modifications through histone methylation (H3K9me3) and deacetylation (H3K18ac) in LPS-activated spleen cells. Collectively, our results suggest that ()-SFN could be a promising epinutraceutical compound for the management of immunoinflammatory diseases.

摘要

本研究的目的是在脂多糖(LPS)刺激的小鼠腹腔巨噬细胞体外模型中,探究天然对映体()-萝卜硫素(SFN)的免疫调节作用以及可能涉及的信号通路。此外,我们研究了()-SFN诱导的表观遗传变化以及LPS刺激后小鼠脾细胞中细胞因子产生相关的组蛋白H3的翻译后修饰(H3K9me3和H3K18ac)。()-SFN能够通过下调促炎酶(诱导型一氧化氮合酶、环氧化酶-2和微粒体前列腺素E合酶-1)的表达,抑制活性氧(ROS)、一氧化氮(NO)和细胞因子(白细胞介素-1β、白细胞介素-6、白细胞介素-17、白细胞介素-18和肿瘤坏死因子-α)的产生,从而调节LPS刺激的小鼠腹腔巨噬细胞中的炎症反应和氧化应激。我们还发现,Nrf-2/HO-1轴的激活以及JAK2/STAT-3、丝裂原活化蛋白激酶、经典和非经典炎性小体信号通路的抑制可能是()-SFN免疫调节作用的原因。此外,()-SFN通过LPS激活的脾细胞中的组蛋白甲基化(H3K9me3)和去乙酰化(H3K18ac)调节表观遗传修饰。总的来说,我们的结果表明,()-SFN可能是一种用于管理免疫炎症性疾病的有前景的表观营养化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84f6/9414446/470f2d44c942/pharmaceuticals-15-00966-g010.jpg
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