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S100A8/A9 在炎症中的作用。

S100A8/A9 in Inflammation.

机构信息

Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Xiangya School of Medicine, Cancer Research Institute, Central South University, Changsha, China.

出版信息

Front Immunol. 2018 Jun 11;9:1298. doi: 10.3389/fimmu.2018.01298. eCollection 2018.

Abstract

S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca binding proteins belonging to the S100 family. They often exist in the form of heterodimer, while homodimer exists very little because of the stability. S100A8/A9 is constitutively expressed in neutrophils and monocytes as a Ca sensor, participating in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, S100A8/A9 is released actively and exerts a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate biomarker for diagnosis and follow-up as well as a predictive indicator of therapeutic responses to inflammation-associated diseases. As blockade of S100A8/A9 activity using small-molecule inhibitors or antibodies improves pathological conditions in murine models, the heterodimer has potential as a therapeutic target. In this review, we provide a comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 and highlight its application as a diagnostic and therapeutic target in inflammation-associated diseases.

摘要

S100A8 和 S100A9(分别也称为 MRP8 和 MRP14)是属于 S100 家族的 Ca 结合蛋白。它们通常以异二聚体的形式存在,而由于稳定性,同二聚体很少存在。S100A8/A9 作为 Ca 传感器在中性粒细胞和单核细胞中持续表达,参与细胞骨架重排和花生四烯酸代谢。在炎症过程中,S100A8/A9 被主动释放,并通过刺激白细胞募集和诱导细胞因子分泌来在调节炎症反应中发挥关键作用。S100A8/A9 可用作诊断和随访的候选生物标志物,以及炎症相关疾病治疗反应的预测指标。由于使用小分子抑制剂或抗体阻断 S100A8/A9 的活性可改善小鼠模型中的病理状况,因此该异二聚体具有作为治疗靶点的潜力。在这篇综述中,我们全面详细地介绍了 S100A8/A9 的分布和生物学功能,并强调了其在炎症相关疾病中的诊断和治疗靶点的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ade/6004386/f19d7f3287e6/fimmu-09-01298-g001.jpg

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