PURPOSE The C-X-C motif chemokine ligand 10 (CXCL10) participates in diabetes and diabetic cardiomyopathy development from the early stages. Rosiglitazone (RGZ) exhibits anti-inflammatory properties and can target cardiomyocytes secreting CXCL10, under interferon (IFN)γ and tumor necrosis factor (TNF)α challenge. Cardiomyocyte remodeling, CD4 + T cells and dendritic cells (DCs) significantly contribute to the inflammatory milieu underlying and promoting disease development. We aimed to study the effect of RGZ onto inflammation-induced secretion of CXCL10, IFNγ, TNFα, interleukin (IL)-6 and IL-8 by human CD4 + T and DCs, and onto IFNγ/TNFα-dependent signaling in human cardiomyocytes associated with chemokine release. METHODS Cells maintained within an inflammatory-like microenvironment were exposed to RGZ at near therapy dose (5 µM). ELISA quantified cytokine secretion; qPCR measured mRNA expression; Western blot analyzed protein expression and activation; immunofluorescent analysis detected intracellular IFNγ/TNFα-dependent trafficking. RESULTS In human CD4 + T cells and DCs, RGZ inhibited CXCL10 release likely with a transcriptional mechanism, and reduced TNFα only in CD4 + T cells. In human cardiomyocytes, RGZ impaired IFNγ/TNFα signal transduction, blocking the phosphorylation/nuclear translocation of signal transducer and activator of transcription 1 (Stat1) and nuclear factor-kB (NF-kB), in association with a significant decrease in CXCL10 expression, IL-6 and IL-8 release. CONCLUSION As the combination of Th1 biomarkers like CXCL10, IL-8, IL-6 with classical cardiovascular risk factors seems to improve the accuracy in predicting T2D and coronary events, future studies might be desirable to further investigate the anti-Th1 effect of RGZ.

中文翻译：

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罗格列酮的基于人体细胞的抗炎作用。

目的 CXC 基序趋化因子配体 10 (CXCL10) 从早期参与糖尿病和糖尿病性心肌病的发展。罗格列酮 (RGZ) 具有抗炎特性，可在干扰素 (IFN)γ 和肿瘤坏死因子 (TNF)α 攻击下靶向分泌 CXCL10 的心肌细胞。心肌细胞重塑、CD4 + T 细胞和树突状细胞 (DC) 显着促成了炎症环境的潜在和促进疾病发展。我们旨在研究 RGZ 对炎症诱导的人 CD4 + T 和 DC 分泌 CXCL10、IFNγ、TNFα、白细胞介素 (IL)-6 和 IL-8 的影响，以及对人心肌细胞中 IFNγ/TNFα 依赖性信号传导的影响。随着趋化因子的释放。方法 维持在炎症样微环境中的细胞以接近治疗剂量 (5 µM) 暴露于 RGZ。ELISA量化的细胞因子分泌；qPCR 测量 mRNA 表达；蛋白质印迹分析蛋白质表达和活化；免疫荧光分析检测到细胞内 IFNγ/TNFα 依赖性运输。结果 在人 CD4 + T 细胞和 DCs 中，RGZ 可能通过转录机制抑制 CXCL10 的释放，并且仅在 CD4 + T 细胞中减少 TNFα。在人心肌细胞中，RGZ 损害 IFNγ/TNFα 信号转导，阻断信号转导和转录激活因子 1 (Stat1) 和核因子-kB (NF-kB) 的磷酸化/核转位，与 CXCL10 表达的显着降低相关， IL-6 和 IL-8 释放。结论 由于 CXCL10、IL-8、IL-6 等 Th1 生物标志物与经典心血管危险因素的组合似乎可以提高预测 T2D 和冠状动脉事件的准确性，