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人羊膜间充质干细胞对肝硬化腹水 LPS 刺激的反应:FOXO1 基因和 Th17 激活增强抗菌激活。

Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation.

机构信息

Ri.MED Foundation, 90127 Palermo, Italy.

Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy.

出版信息

Int J Mol Sci. 2024 Feb 28;25(5):2801. doi: 10.3390/ijms25052801.

DOI:10.3390/ijms25052801
PMID:38474048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10932448/
Abstract

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.

摘要

自发性细菌性腹膜炎 (SBP) 是失代偿期肝硬化患者的严重并发症,通常采用广谱抗生素治疗。然而,抗生素耐药性的上升要求采用替代的治疗策略。最近的研究表明,人羊膜间充质干细胞 (hA-MSCs) 在体外能够促进细菌清除,并调节 SBP 中的免疫和炎症反应。我们的结果突出显示 hA-MSCs 中 FOXO1、CXCL5、CXCL6、CCL20 和 MAPK13 的上调,以及在 72 小时治疗后促进细菌清除,促使免疫反应向 Th17 淋巴细胞表型转变。在这项研究中,我们使用了体外 SBP 模型,并采用组学技术(下一代测序)来研究 hA-MSCs 改变 LPS 刺激腹水免疫细胞间串扰的机制。我们还通过 qRT-PCR、细胞荧光分析和 Luminex 检测验证了数据。这些发现为使用 hA-MSCs 预防和治疗感染性疾病(如 SBP)提供了进一步的支持,为抗生素治疗提供了一种可行的替代方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/1b7c466affb2/ijms-25-02801-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/a17a8204f4f4/ijms-25-02801-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/592c70a0823d/ijms-25-02801-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/90f55b87a373/ijms-25-02801-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/14a827cb973c/ijms-25-02801-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/1128de71859e/ijms-25-02801-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/99c8da85a2a2/ijms-25-02801-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/1b7c466affb2/ijms-25-02801-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/a17a8204f4f4/ijms-25-02801-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/592c70a0823d/ijms-25-02801-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/7fb11b1bd188/ijms-25-02801-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/635e6d4ae8ea/ijms-25-02801-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/90f55b87a373/ijms-25-02801-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/14a827cb973c/ijms-25-02801-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/1128de71859e/ijms-25-02801-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/99c8da85a2a2/ijms-25-02801-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f2/10932448/1b7c466affb2/ijms-25-02801-g009.jpg

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本文引用的文献

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