Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, the Netherlands.
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, the Netherlands.
Pharmacol Res. 2021 Jan;163:105236. doi: 10.1016/j.phrs.2020.105236. Epub 2020 Oct 11.
Regulation of inflammation is a central part of the maintenance of homeostasis by the immune system. One important class of regulatory protein that has been shown to have effects on the inflammatory process are the 14-3-3 proteins. Herein we describe the roles that have been identified for 14-3-3 in regulation of the inflammatory response. These roles encompass regulation of the response that affect inflammation at the genetic, molecular and cellular levels. At a genetic level 14-3-3 is involved in the regulation of multiple transcription factors and affects the transcription of key effectors of the immune response. At a molecular level many of the constituent parts of the inflammatory process, such as pattern recognition receptors, protease activated receptors and cytokines are regulated through phosphorylation and recognition by 14-3-3 whilst disruption of the recognition processes has been observed to result in clinical syndromes. 14-3-3 is also involved in the regulation of cell proliferation and differentiation, this has been shown to affect the immune system, particularly T- and B-cells. Finally, we discuss how abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.
炎症的调控是免疫系统维持内稳态的核心部分。已有研究表明，14-3-3 蛋白是一类对炎症过程具有重要作用的调节蛋白。本文介绍了 14-3-3 在炎症反应调控中的作用。这些作用涵盖了在基因、分子和细胞水平上影响炎症的反应调控。在基因水平上，14-3-3 参与了多个转录因子的调控，影响了免疫反应关键效应因子的转录。在分子水平上，炎症过程的许多组成部分，如模式识别受体、蛋白酶激活受体和细胞因子，通过磷酸化和 14-3-3 的识别进行调节，而识别过程的中断已被观察到导致临床综合征。14-3-3 还参与细胞增殖和分化的调控，这已被证明会影响免疫系统，特别是 T 细胞和 B 细胞。最后，我们讨论了 14-3-3 水平异常如何导致不良的免疫反应和慢性炎症状态。
