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巨噬细胞标志物转位蛋白(TSPO)在促炎性“M1”型人类巨噬细胞上表达下调。

The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory 'M1' human macrophages.

作者信息

Narayan Nehal, Mandhair Harpreet, Smyth Erica, Dakin Stephanie Georgina, Kiriakidis Serafim, Wells Lisa, Owen David, Sabokbar Afsie, Taylor Peter

机构信息

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Headington, Oxford, United Kingdom.

Imanova Centre for Imaging Sciences, Hammersmith, London, United Kingdom.

出版信息

PLoS One. 2017 Oct 2;12(10):e0185767. doi: 10.1371/journal.pone.0185767. eCollection 2017.

Abstract

The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or 'M1' phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages.

摘要

转位蛋白(TSPO)是一种线粒体膜蛋白,其功能尚不确定。据称它在活化巨噬细胞上高表达,这使得以正电子发射断层扫描(PET)形式的TSPO靶向分子成像可用于检测和量化体内炎症。然而,关于TSPO在人类活化巨噬细胞上表达的现有文献较少,大多来自脑组织研究,包括脑恶性肿瘤以及多发性硬化症等炎症性疾病的研究。在此,我们利用来自THP-1单核细胞、健康外周血单核细胞以及类风湿性关节炎患者滑液单核细胞这三种人类来源的单核细胞衍生巨噬细胞(MDM),对活化巨噬细胞中TSPO的表达进行了详细研究。在这项工作中,我们证明了被激活为促炎或“M1”表型的巨噬细胞中TSPO mRNA和蛋白持续下调。相反,用IL-4、地塞米松或TGF-β1将巨噬细胞刺激为M2表型,无论MDM来源如何,都不会改变TSPO的表达。其原因尚不确定,但我们的研究结果为最近关于TSPO可能参与巨噬细胞炎症反应负调控的研究结论提供了一些支持证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e861/5624624/572b07f37e8c/pone.0185767.g001.jpg

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