Models for the Study of the Cross Talk Between Inflammation and Cell Cycle
Models for the Study of the Cross Talk Between Inflammation and Cell Cycle
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DOI：
10.1007/978-1-4939-2926-9_15
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发表时间：
2016-01-01
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影响因子：
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通讯作者：
Rossi, Adriano G.
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文献类型：
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作者：
Hoodless, Laura J.;Robb, Calum T.;Rossi, Adriano G.
细胞周期蛋白依赖性激酶（CDK）传统上与细胞周期相关。然而，现在已知CDK 7和CDK 9通过RNA聚合酶II的磷酸化和随后的例如炎性介质和影响凋亡过程的因子的合成来调节转录活性;包括粒细胞如嗜中性粒细胞和嗜酸性粒细胞的凋亡。炎症的成功消退和正常组织稳态的恢复需要这些炎性细胞的凋亡和随后通过吞噬细胞如巨噬细胞清除凋亡小体。据信，CDK 7和CDK 9的影响，因为他们参与了抗凋亡蛋白，如Mcl-1，这是特别重要的粒细胞survival.This章介绍了各种体外和体内模型，用于调查CDKs和他们的抑制剂在粒细胞，特别是CDKs在细胞凋亡途径中的作用的转录炎症的决议。这可以通过分离和使用原代粒细胞在体外进行，以及使用啮齿动物和斑马鱼中的炎性疾病的动物模型在体内进行。本文描述的评估CDK在炎症和细胞凋亡中的作用的一些方法包括流式细胞术和蛋白质印迹，以及固定组织中细胞凋亡的成像和定量，以及体内炎症模型。
Cyclin-dependent kinases (CDKs) have been traditionally associated with the cell cycle. However, it is now known that CDK7 and CDK9 regulate transcriptional activity via phosphorylation of RNA polymerase II and subsequent synthesis of, for example, inflammatory mediators and factors that influence the apoptotic process; including apoptosis of granulocytes such as neutrophils and eosinophils. Successful resolution of inflammation and restoration of normal tissue homeostasis requires apoptosis of these inflammatory cells and subsequent clearance of apoptotic bodies by phagocytes such as macrophages. It is believed that CDK7 and CDK9 influence resolution of inflammation since they are involved in the transcription of antiapoptotic proteins such as Mcl-1 which is especially important in granulocyte survival.This chapter describes various in vitro and in vivo models used to investigate CDKs and their inhibitors in granulocytes and particularly the role of CDKs in the apoptosis pathway. This can be performed in vitro by isolation and use of primary granulocytes and in vivo using animal models of inflammatory disease in rodents and zebrafish. Some of the methods described here to assess the role of CDKs in inflammation and apoptosis include flow cytometry and western blotting, together with imaging and quantification of apoptosis in fixed tissue, as well as in vivo models of inflammation.