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耐受原性益生菌 德氏乳杆菌和鼠李糖乳杆菌促进系统性红斑狼疮初诊患者巨噬细胞来源的单核细胞的抗炎表型。

Tolerogenic probiotics Lactobacillus delbrueckii and Lactobacillus rhamnosus promote anti-inflammatory profile of macrophages-derived monocytes of newly diagnosed patients with systemic lupus erythematosus.

机构信息

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Cell Biochem Funct. 2024 Mar;42(2):e3981. doi: 10.1002/cbf.3981.

Abstract

Systemic lupus erythematosus (SLE) is known as an autoimmune disorder that is characterized by the breakdown of self-tolerance, resulting in disease onset and progression. Macrophages have been implicated as a factor in the development of SLE through faulty phagocytosis of dead cells or an imbalanced M1/M2 ratio. The study aimed to investigate the immunomodulatory effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on M1 and M2 macrophages in new case lupus patients. For this purpose, blood monocytes were collected from lupus patients and healthy people and were cultured for 5 days to produce macrophages. For 48 h, the macrophages were then cocultured with either probiotics or lipopolysaccharides (LPS). Flow cytometry and real-time polymerase chain reaction were then used to analyze the expression of cluster of differentiation (CD) 14, CD80, and human leukocyte antigen - DR (HLADR) markers, as well as cytokine expression (interleukin [IL]1-β, IL-12, tumor necrosis factor α [TNF-α], IL-10, and transforming growth factor beta [TGF-β]). The results indicated three distinct macrophage populations, M0, M1, and M2. In both control and patient-derived macrophage-derived monocytes (MDMs), the probiotic groups showed a decrease in CD14, CD80, and HLADR expression compared to the LPS group. This decrease was particularly evident in M0 and M2 macrophages from lupus patients and M1 macrophages from healthy subjects. In addition, the probiotic groups showed increased levels of IL-10 and TGF-β and decreased levels of IL-12, IL1-β, and TNF-α in MDMs from both healthy and lupus subjects compared to the LPS groups. Although there was a higher expression of pro-inflammatory cytokines in lupus patients, there was a higher expression of anti-inflammatory cytokines in healthy subjects. In general, L. delbrueckii and L. rhamnosus could induce anti-inflammatory effects on MDMs from both healthy and lupus subjects.

摘要

系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征是自身耐受性的破坏,导致疾病的发生和进展。巨噬细胞被认为是 SLE 发展的一个因素,通过对死亡细胞的吞噬作用失常或 M1/M2 比例失衡。本研究旨在探讨德氏乳杆菌和鼠李糖乳杆菌对新发病例狼疮患者 M1 和 M2 巨噬细胞的免疫调节作用。为此,从狼疮患者和健康人采集血液单核细胞,并培养 5 天以产生巨噬细胞。然后,将巨噬细胞与益生菌或脂多糖(LPS)共培养 48 小时。然后使用流式细胞术和实时聚合酶链反应分析分化群(CD)14、CD80 和人类白细胞抗原-DR(HLADR)标志物的表达以及细胞因子表达(白细胞介素[IL]1-β、IL-12、肿瘤坏死因子α[TNF-α]、IL-10 和转化生长因子β[TGF-β])。结果表明存在三种不同的巨噬细胞群体,M0、M1 和 M2。在对照和患者来源的巨噬细胞衍生单核细胞(MDM)中,与 LPS 组相比,益生菌组的 CD14、CD80 和 HLADR 表达均降低。这种降低在狼疮患者的 M0 和 M2 巨噬细胞以及健康受试者的 M1 巨噬细胞中尤为明显。此外,与 LPS 组相比,益生菌组在健康受试者和狼疮患者的 MDM 中表现出更高水平的 IL-10 和 TGF-β以及更低水平的 IL-12、IL1-β 和 TNF-α。尽管狼疮患者中促炎细胞因子的表达较高,但健康受试者中抗炎细胞因子的表达较高。总的来说,德氏乳杆菌和鼠李糖乳杆菌可以诱导健康受试者和狼疮患者的 MDM 产生抗炎作用。

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