Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes.

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in bioscience (Landmark edition) Pub Date : 2024-02-22 DOI:10.31083/j.fbl2902085

Liang Yang, Yuxuan Qian, Shixin Lei, Dongping Sun

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引用次数: 0

Abstract

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause immune response in TIDM are still under investigation. Therefore, the goal of this study was to investigate the role of advanced glycation end products (AGEs) in the regulation of the immune response in peripheral blood mononuclear cells (PBMCs) from patients with T1DM.

Methods: PBMCs isolated from T1DM patients and control subjects were used in the current study. Cytokines, AGEs related to glyoxalase 1 (GLO1), methylglyoxal (MG)-derived AGEs were assessed longitudinally.

Results: The results of published T1DM PBMC microarray datasets using random-effects meta-analysis models revealed immune responses in the PBMCs of patients with T1DM compared with control subjects. Moreover, the activity of GLO1, which is the key MG-metabolizing enzyme, was significantly reduced in PBMCs from T1DM patients. We confirmed that, compared to the control subjects, GLO1 expression and activity were markedly decreased and MG-derived AGEs were significantly accumulated in the PBMCs from T1DM patients. In addition, phytohemagglutinin stimulated the secretion of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) was positively correlated with the accumulation of cellular AGEs. Therefore, the exposure of PBMCs from control subjects to MG and a GLO1 inhibitor enhanced the accumulation of cellular MG-derived AGEs and the secretion of TNF-α and IFN-γ.

Conclusions: The results of this study showed that the accumulation of cellular AGEs causes a decline in the immune response of patients with T1DM.

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细胞高级糖化终产物会加重 1 型糖尿病患者单核细胞的免疫反应。

背景：1 型糖尿病（T1DM）是一种以免疫反应介导的胰岛β细胞破坏为特征的自身免疫性疾病。然而，导致 T1DM 免疫反应的机制仍在研究之中。因此，本研究旨在探讨高级糖化终产物（AGEs）在调节 T1DM 患者外周血单核细胞（PBMCs）免疫反应中的作用：方法：本研究使用了从 T1DM 患者和对照组中分离的外周血单核细胞。纵向评估细胞因子、与乙醛醛酶 1（GLO1）相关的 AGEs、甲基乙二醛（MG）衍生的 AGEs：使用随机效应荟萃分析模型对已发表的 T1DM PBMC 芯片数据集进行分析的结果显示，与对照组相比，T1DM 患者的 PBMC 中存在免疫反应。此外，在 T1DM 患者的 PBMCs 中，MG 关键代谢酶 GLO1 的活性明显降低。我们证实，与对照组相比，T1DM 患者的 PBMCs 中 GLO1 的表达和活性明显降低，MG 衍生的 AGEs 明显累积。此外，植物血凝素能刺激肿瘤坏死因子α（TNF-α）的分泌，而γ干扰素（IFN-γ）与细胞AGEs的积累呈正相关。因此，将对照组受试者的 PBMC 暴露于 MG 和 GLO1 抑制剂会增强细胞 MG 衍生 AGEs 的积累以及 TNF-α 和 IFN-γ 的分泌：本研究结果表明，细胞 AGEs 的积累会导致 T1DM 患者的免疫反应下降。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in bioscience (Landmark edition)

CiteScore

3.50

自引率

0.00%

发文量