Extracellular cyclophilins in health and disease.
Extracellular cyclophilins in health and disease.
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DOI：
10.1016/j.bbagen.2014.11.013
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发表时间：
2015-10
影响因子：
3
通讯作者：
Bukrinsky, Michael
中科院分区：
文献类型：
--
作者：
Bukrinsky, Michael
细胞外亲环蛋白（eCyPs）是参与许多炎性疾病发病机制的促炎因子。eCyP的大部分致病活性与其对白细胞的趋化作用有关，这种趋化作用是由靶细胞上的eCyP受体CD147介导的，并涉及亲环蛋白的肽酰脯氨酸顺式反式异构酶活性。这种活性被环孢素A （CsA）和这种药物的非免疫抑制衍生物所抑制。越来越多关于eCyPs在疾病发病机制中的作用的证据刺激了对ecyp启动事件机制的研究，从而确定了多种信号通路，表征了ecyp处理细胞释放的各种效应分子，并合成了特异性阻断eCyPs的CsA衍生物。然而，与eCyPs的作用方式有关的一些重要问题仍未得到解答。在本文中，我们将细胞外亲环蛋白的释放和功能的现有信息整合到一个统一的模型中，重点关注需要澄清的突出问题。细胞外亲环蛋白在许多炎症性疾病的发病机制中起着关键作用。它们的作用机制包括与受体CD147相互作用，并启动一个特征不明确的信号转导过程，最终导致趋化和促炎因子的产生。细胞外亲环蛋白是治疗干预的一个有吸引力的靶点，可用于减轻急性和慢性炎症的症状和后果。这篇文章是《脯氨酸定向折叠酶：细胞信号传导催化剂和药物靶点》特刊的一部分。细胞释放的亲环蛋白家族的三个成员是CyPA、CyPB和CyPC。CyPA的分泌可能受乙酰化调节。细胞外亲环蛋白A和B是促炎因子。抑制细胞外CyPA或其受体CD147可减轻炎症。CsA的细胞不渗透性衍生物是一种很有前途的抗炎药。
Extracellular cyclophilins (eCyPs) are pro-inflammatory factors implicated in pathogenesis of a number of inflammatory diseases. Most pathogenic activities of eCyPs are related to their chemotactic action towards leukocytes, which is mediated by eCyP receptor on target cells, CD147, and involves peptidyl–prolyl cis–trans isomerase activity of cyclophilins. This activity is inhibited by cyclosporine A (CsA) and non-immunosuppressive derivatives of this drug. Accumulating evidence for the role of eCyPs in disease pathogenesis stimulated research on the mechanisms of eCyP-initiated events, resulting in identification of multiple signaling pathways, characterization of a variety of effector molecules released from eCyP-treated cells, and synthesis of CsA derivatives specifically blocking eCyPs. However, a number of important questions related to the mode of action of eCyPs remain unanswered. In this article, we integrate available information on release and function of extracellular cyclophilins into a unified model, focusing on outstanding issues that need to be clarified. Extracellular cyclophilins are critical players in pathogenesis of a number of inflammatory diseases. Their mechanism of action involves interaction with the receptor, CD147, and initiation of a poorly characterized signal transduction process culminating in chemotaxis and production of pro-inflammatory factors. Extracellular cyclophilins present an attractive target for therapeutic interventions that can be used to alleviate symptoms and consequences of acute and chronic inflammation. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets. Three members of the cyclophilin family released from cells are CyPA, CyPB and CyPC. CyPA secretion may be regulated by acetylation. Extracellular cyclophilins A and B are pro-inflammatory factors. Inhibition of extracellular CyPA or its receptor, CD147, reduces inflammation. Cell-impermeable derivative of CsA is a promising anti-inflammatory agent.
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影响因子：
4.5
作者：
Cabral WA;Perdivara I;Weis M;Terajima M;Blissett AR;Chang W;Perosky JE;Makareeva EN;Mertz EL;Leikin S;Tomer KB;Kozloff KM;Eyre DR;Yamauchi M;Marini JC
通讯作者：
Marini JC
影响因子：
20.3
作者：
Cho, JY;Fox, DA;Chain, B
通讯作者：
Chain, B
影响因子：
4.5
作者：
Choi JW;Sutor SL;Lindquist L;Evans GL;Madden BJ;Bergen HR 3rd;Hefferan TE;Yaszemski MJ;Bram RJ
通讯作者：
Bram RJ
影响因子：
3.4
作者：
Chevalier, Francois;Depagne, Jordane;Lebeau, Jerome
通讯作者：
Lebeau, Jerome
影响因子：
4.4
作者：
Arora, K;Gwinn, WM;Constant, SL
通讯作者：
Constant, SL