强直性脊柱炎患者中MPO表达上调与细胞因子失衡的显著相关性以及间充质干细胞介导的抑制作用。

Significant correlations of upregulated MPO expression with cytokine imbalance in ankylosing spondylitis patients and the inhibitory effect mediated by mesenchymal stem cells.

作者信息

Liu Shubei, Yang Chunjuan, Xu Donghua, Gu Bingjie, Shen Minning

机构信息

Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.

Department of Rheumatology and Immunology, Weifang People's Hospital, Shandong Second Medical University, Weifang, 261000, China.

出版信息

BMC Musculoskelet Disord. 2025 Mar 1;26(1):212. doi: 10.1186/s12891-025-08458-6.

DOI:10.1186/s12891-025-08458-6

PMID:40022014

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11871679/

Abstract

BACKGROUND

Little is known regarding both the role of myeloperoxidase (MPO) and the impact of mesenchymal stem cells (MSCs) on inflammatory and immune responses in ankylosing spondylitis (AS). This study is aimed to explore the role of MPO and the regulatory effect of umbilical cord-derived MSCs on MPO expression in monocytes in AS.

METHODS

MPO mRNA expression in the peripheral blood mononuclear cells (PBMCs) was detected by Real-time PCR. Cytokines including IL-2, IFN-γ, IL-17 A, IL-4, IL-10, IL-6 and TNF-α were determined by flow cytometry. A co-culture system was established by culturing THP-1 cells with MSCs at a ratio of 5:1.

RESULTS

Increased mRNA expression of MPO was observed in PBMCs of AS patients compared to healthy controls (P < 0.05). The mRNA expression of MPO was positively associated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (P < 0.05) in AS. Besides, the levels of IL-2, IL-10, IFN-γ, IL-17 A, IL-4, IL-6, TNF-α in plasma were notably increased in AS (P < 0.05). Positive correlations between MPO expression and IL-2, IFN -γ, IL-4, TNF-α as well as IL-6 were demonstrated in AS (P < 0.05). Furthermore, MSCs remarkably suppressed the mRNA expression of MPO along with the secretion of IL-17 A and TNF-α, but promoted IL-10 generation in monocytes.

CONCLUSION

MPO expression is significantly upregulated and correlates with cytokine imbalance in AS. It may serve as a valuable immunotherapeutic target for AS. MSCs can significantly inhibit monocyte-mediated inflammatory response potentially by downregulating MPO in monocytes.

摘要

背景

关于髓过氧化物酶（MPO）的作用以及间充质干细胞（MSCs）对强直性脊柱炎（AS）炎症和免疫反应的影响，目前了解甚少。本研究旨在探讨MPO在AS中的作用以及脐带间充质干细胞对AS患者单核细胞中MPO表达的调节作用。

方法

采用实时荧光定量PCR检测外周血单个核细胞（PBMCs）中MPO mRNA的表达。采用流式细胞术检测白细胞介素-2（IL-2）、干扰素-γ（IFN-γ）、白细胞介素-17A（IL-17A）、白细胞介素-4（IL-4）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等细胞因子。以5:1的比例将THP-1细胞与间充质干细胞共培养，建立共培养体系。

结果

与健康对照组相比，AS患者PBMCs中MPO的mRNA表达增加（P < 0.05）。在AS中，MPO的mRNA表达与C反应蛋白（CRP）和红细胞沉降率（ESR）呈正相关（P < 0.05）。此外，AS患者血浆中IL-2、IL-10、IFN-γ、IL-17A、IL-4、IL-6、TNF-α水平显著升高（P < 0.05）。在AS中，MPO表达与IL-2、IFN-γ、IL-4、TNF-α以及IL-6之间呈正相关（P < 0.05）。此外，间充质干细胞显著抑制MPO的mRNA表达以及IL-17A和TNF-α的分泌，但促进单核细胞中IL-10的生成。