在脓毒症相关心肾综合征中,硫化氢通过PINK1/帕金森介导的有丝分裂调节巨噬细胞表型变化的潜在作用。

IF 2.9 4区 医学 Q3 IMMUNOLOGY Immunopharmacology and Immunotoxicology Pub Date : 2024-04-01 Epub Date: 2023-11-16 DOI:10.1080/08923973.2023.2281901
Yuxuan Chen, Wei Cao, Bin Li, Xiaofei Qiao, Xiangdong Wang, Guang Yang, Siying Li
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引用次数: 0

摘要

目的:脓毒症是5型心肾综合征(CRS-5)的主要原因之一,导致不可逆的组织损伤和器官功能障碍。巨噬细胞已被证明在脓毒症的病理生理中发挥关键作用,强调需要确定脓毒症中调节巨噬细胞表型的治疗靶点。方法与结果:本研究研究了一种快速释放的硫化氢(H2S)供体NaSH和一种从大蒜中提取的缓释硫化氢化合物s -丙炔半胱氨酸(SPRC)对巨噬细胞的免疫调节作用。NaSH和SPRC显示出保护心脏和肾脏免受LPS诱导的组织损伤的潜力。免疫组化F4/80+显示,NaSH和SPRC可减少lps处理小鼠心脏和肾脏组织中巨噬细胞的浸润。此外,在lps触发的RAW264.7巨噬细胞炎症级联中,NaSH和SPRC对炎症细胞因子的分泌、活性氧(ROS)的产生以及巨噬细胞表型从m1样向m2样的调节均有显著抑制作用。此外,在LPS刺激下,NaSH和SPRC可诱导自噬,这是氧化应激和免疫反应中受损蛋白和细胞器消除的关键过程。结果,线粒体数量增加,线粒体膜电位改善。这一过程主要通过PINK1/Parkin通路介导的有丝分裂介导。讨论:这些结果表明H2S供体的免疫调节作用是通过PINK1/ parkinson介导的线粒体自噬途径进行的。总之,我们的研究为脂多糖性心肾损伤的治疗提供了新的方向。
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The potential role of hydrogen sulfide in regulating macrophage phenotypic changes via PINK1/parkin-mediated mitophagy in sepsis-related cardiorenal syndrome.

Objective: Sepsis is one of major reasons of cardiorenal syndrome type 5 (CRS-5), resulting in irreversible tissue damage and organ dysfunction. Macrophage has been demonstrated to play key role in the pathophysiology of sepsis, highlighting the need to identify therapeutic targets for modulating macrophage phenotype in sepsis.

Methods and results: In this study, a rapid-releasing hydrogen sulfide (H2S) donor NaSH, and a slow-releasing H2S compound S-propargyl-cysteine (SPRC) which is derived from garlic, have been studied for the immune-regulatory effects on macrophages. The NaSH and SPRC showed the potential to protect the heart and kidney from tissue injury induced by LPS. The immunohistochemistry of F4/80+ revealed that the infiltration of macrophages in the heart and kidney tissues of LPS-treated mice was reduced by NaSH and SPRC. In addition, in the LPS-triggered inflammatory cascade of RAW264.7 macrophage cells, NaSH and SPRC exhibited significantly inhibitory effects on the secretion of inflammatory cytokines, production of reactive oxygen species (ROS), and regulation of the macrophage phenotype from M1-like to M2-like. Moreover, autophagy, a crucial process involved in the elimination of impaired proteins and organelles during oxidative stress and immune response, was induced by NaSH and SPRC in the presence of LPS stimulation. Consequently, there was an increase in the number of mitochondria and an improvement in mitochondrial membrane potential. This process was mainly mediated by PINK1/Parkin pathway mediated mitophagy.

Discussion: These results demonstrated that the immunoregulatory effects of H2S donors were through the PINK1/Parkin-mediated mitophagy pathway. Overall, our study provided a new therapeutic direction in LPS-induced cardiorenal injury.

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来源期刊
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).
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