S100A8 / A9：从基础科学到临床应用。,Pharmacology & Therapeutics

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S100A8 / A9：从基础科学到临床应用。
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2016-08-06 , DOI: 10.1016/j.pharmthera.2016.07.015
Monika Pruenster ₁ , Thomas Vogl ₂ , Johannes Roth ₂ , Markus Sperandio ₁

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中性粒细胞和单核细胞属于免疫防御细胞的第一线，在感染或无菌性损伤期间被募集到炎症部位。两种细胞在其细胞质中均含有大量的异二聚体蛋白S100A8 / A9。S100A8 / A9属于与Ca2 +结合的S100蛋白家族，近来作为调节其从嗜中性粒细胞和单核细胞释放（细胞外S100A8 / A9）后炎症反应的关键警报蛋白，引起了广泛的关注。细胞外S100A8 / A9与模式识别受体Toll样受体4（TLR4）和高级糖基化终产物受体（RAGE）相互作用，促进细胞活化和募集。除了其生物学功能外，S100A8 / A9（也称为髓样相关蛋白8/14，MRP8 / 14）被认为是监测慢性炎症疾病（包括炎症性肠病和类风湿关节炎）中疾病活动的有趣生物标志物。此外，S100A8 / A9已在临床前成像研究中成功测试以定位感染或无菌损伤的部位。最后，使用S100A8 / A9小分子抑制剂的最新证据还表明，在包括多发性硬化症，系统性红斑狼疮，类风湿性关节炎和炎症性肠病在内的自身免疫性疾病的动物模型中，阻断S100A8 / A9的活性会对疾病活动产生有益的影响。这篇综述将提供有关S100A8 / A9的结构和生物学功能的全面详细的概述，还将针对针对S100A8 / A9的诊断和治疗应用提供一个展望。

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S100A8/A9: From basic science to clinical application.

Neutrophils and monocytes belong to the first line of immune defence cells and are recruited to sites of inflammation during infection or sterile injury. Both cells contain huge amounts of the heterodimeric protein S100A8/A9 in their cytoplasm. S100A8/A9 belongs to the Ca2+ binding S100 protein family and has recently gained a lot of interest as a critical alarmin modulating the inflammatory response after its release (extracellular S100A8/A9) from neutrophils and monocytes. Extracellular S100A8/A9 interacts with the pattern recognition receptors Toll-like receptor 4 (TLR4) and Receptor for Advanced Glycation Endproducts (RAGE) promoting cell activation and recruitment. Besides its biological function, S100A8/A9 (also known as myeloid related protein 8/14, MRP8/14) was identified as interesting biomarker to monitor disease activity in chronic inflammatory disorders including inflammatory bowel disease and rheumatoid arthritis. Furthermore, S100A8/A9 has been tested successfully in pre-clinical imaging studies to localize sites of infection or sterile injury. Finally, recent evidence using small molecule inhibitors for S100A8/A9 also suggests that blocking S100A8/A9 activity exerts beneficial effects on disease activity in animal models of autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. This review will provide a comprehensive and detailed overview into the structure and biological function of S100A8/A9 and also will give an outlook in terms of diagnostic and therapeutic applications targeting S100A8/A9.

更新日期：2016-08-01

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