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血清中高水平的白细胞介素-1β可诱导 hUC-MSCs 中白细胞介素-8 的表达增加，降低 hUC-MSCs 治疗肝衰竭的疗效。

The high level of IL-1β in the serum of ACLF patients induces increased IL-8 expression in hUC-MSCs and reduces the efficacy of hUC-MSCs in liver failure.

机构信息

Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.

Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Stem Cell Res Ther. 2023 Aug 30;14(1):231. doi: 10.1186/s13287-023-03455-9.

DOI:10.1186/s13287-023-03455-9
PMID:37649110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10468895/
Abstract

BACKGROUND: Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients' serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs. METHODS: The serum of surviving and dead ACLF patients was collected to culture hUC-MSCs in vitro, and the hUC-MSCs cultured in the serum of ACLF patients were used to treat acute liver failure (ALF) rats. The therapeutic effect on the rats was evaluated by a survival curve, the transaminase level and liver histopathology. The expression of cytokines in hUC-MSCs was detected by Q-PCR and ELISA. RESULTS: Serum pretreatment reduced the therapeutic effect of hUC-MSCs on ALF, especially pretreatment in the serum from dead ACLF patients. After hUC-MSCs were cultured in the serum of surviving or dead ACLF patients, the most differentially expressed factor was IL-8. Interfering with the expression of IL-8 in hUC-MSCs can improve the therapeutic effect of hUC-MSCs on ALF. The high level of IL-1β in the serum of dead ACLF patients causes the increased expression of IL-8 in hUC-MSCs through the activation of the NF-κB signaling pathway. Meanwhile, we found that the neutralizing IL-1β in serum from dead ACLF patients can improve the therapeutic effect of hUC-MSCs on ALF. CONCLUSION: The high level of IL-1β in ACLF serum can promote the expression of IL-8 in hUC-MSCs through the NF-κB signaling pathway, thus reducing the effect of hUC-MSCs on ALF.

摘要

背景：干细胞主要通过免疫调节发挥治疗作用。然而，患者血清中的炎症相关因子可能会影响干细胞的免疫调节功能。因此，本研究旨在探讨慢性加急性肝衰竭（ACLF）患者血清影响人脐带来源间充质干细胞（hUC-MSCs）疗效的可能机制。

方法：收集存活和死亡的 ACLF 患者的血清，在体外培养 hUC-MSCs，并用 ACLF 患者血清培养的 hUC-MSCs 治疗急性肝衰竭（ALF）大鼠。通过生存曲线、转氨酶水平和肝组织病理学评估对大鼠的治疗效果。通过 Q-PCR 和 ELISA 检测 hUC-MSCs 中细胞因子的表达。

结果：血清预处理降低了 hUC-MSCs 对 ALF 的治疗效果，尤其是来自死亡 ACLF 患者的血清预处理。hUC-MSCs 在存活或死亡 ACLF 患者的血清中培养后，表达差异最大的因子是 IL-8。干扰 hUC-MSCs 中 IL-8 的表达可以改善 hUC-MSCs 对 ALF 的治疗效果。死亡 ACLF 患者血清中高浓度的 IL-1β 通过激活 NF-κB 信号通路导致 hUC-MSCs 中 IL-8 的表达增加。同时，我们发现死亡 ACLF 患者血清中的中和 IL-1β 可以改善 hUC-MSCs 对 ALF 的治疗效果。

结论：ACLF 血清中高浓度的 IL-1β 通过 NF-κB 信号通路促进 hUC-MSCs 中 IL-8 的表达，从而降低 hUC-MSCs 对 ALF 的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/99a791d0b393/13287_2023_3455_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/040f4df77593/13287_2023_3455_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/b41ff6287461/13287_2023_3455_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/17e4473aced5/13287_2023_3455_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/b67540bc0180/13287_2023_3455_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/eff211a548b5/13287_2023_3455_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/99a791d0b393/13287_2023_3455_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/040f4df77593/13287_2023_3455_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/b41ff6287461/13287_2023_3455_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/17e4473aced5/13287_2023_3455_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/b67540bc0180/13287_2023_3455_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/eff211a548b5/13287_2023_3455_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3440/10468895/99a791d0b393/13287_2023_3455_Fig6_HTML.jpg

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[2]
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[3]
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[4]
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本文引用的文献

[1]
Interleukin-8: An evolving chemokine.

Cytokine. 2022-5

[2]
Antcin K Inhibits TNF-α, IL-1β and IL-8 Expression in Synovial Fibroblasts and Ameliorates Cartilage Degradation: Implications for the Treatment of Rheumatoid Arthritis.

Front Immunol. 2021

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Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice.

Stem Cell Res Ther. 2021-12-11

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J Leukoc Biol. 2021-9

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Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment.

Int J Mol Sci. 2021-4-13

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Sci Signal. 2021-3-9

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Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis.

Stem Cell Res Ther. 2021-1-9

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Front Immunol. 2020-10-8

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