Differential regulation of fibrinogen γ chain splice isoforms by interleukin-6
Differential regulation of fibrinogen γ chain splice isoforms by interleukin-6
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DOI：
10.1016/j.thromres.2012.09.017
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发表时间：
2013-01-01
影响因子：
7.5
通讯作者：
Farrell, David H.
中科院分区：
文献类型：
--
作者：
Rein-Smith, Chantelle M.;Anderson, Nathan W.;Farrell, David H.
前言：纤维蛋白原是血栓中的主要结构蛋白，也是著名的急性期反应物。纤维蛋白原的伽马链基因有两个选择性剪接变异体，即伽马A链和伽马‘链。γ‘纤维蛋白原约占总纤维蛋白原的7%。总纤维蛋白原水平和γ‘纤维蛋白原水平与心血管疾病有关，但调节这两种异构体产生的机制尚不清楚。已知有几种炎性细胞因子影响总纤维蛋白原的产生，但细胞因子在γ‘纤维蛋白原产生中的作用尚未被研究。材料和方法：经IL-1β、转化生长因子-β、肿瘤坏死因子-α和白细胞介素6处理后，定量检测人肝细胞中γ-纤维蛋白原和总纤维蛋白原的表达。结果：已知的总纤维蛋白原合成的下调因子-白细胞介素1-β、转化生长因子-β和肿瘤坏死因子-α也下调了人肝细胞的γ-纤维蛋白原的合成。然而，IL-6不同程度地上调了总纤维蛋白原和γ‘纤维蛋白原的产生，导致γ-A mRNA增加3.6倍，而γ’mRNA增加8.3倍。结论：IL-6诱导的炎症反应不成比例地上调了γ‘纤维蛋白原。(C)2012爱思唯尔有限公司。保留所有权利。
Introduction: Fibrinogen is a major structural protein in blood clots, and is also a well-known acute phase reactant. The gamma chain gene of fibrinogen has two alternative splice variants, gamma A and gamma' chains. gamma' fibrinogen constitutes about 7% of total fibrinogen. Total fibrinogen levels and gamma' fibrinogen levels have been associated with cardiovascular disease, but the mechanisms regulating the production of the two isoforms are unknown. Several inflammatory cytokines are known to influence the production of total fibrinogen, but the role of cytokines in the production of gamma' fibrinogen has not been examined. However, epidemiologic studies have shown an association between gamma' fibrinogen levels and inflammatory markers in humans.Materials and methods: The expression of gamma fibrinogen and total fibrinogen by HepG2 liver cells was quantitated after treatment with interleukin-1 beta, transforming growth factor-beta, tumor necrosis factor-alpha, and interleukin-6.Results: Interleukin-1 beta, transforming growth factor-beta, and tumor necrosis factor-alpha, known down-regulators of total fibrinogen synthesis, also downregulate gamma' fibrinogen synthesis in HepG2 cells. However, interleukin-6 differentially up-regulates the production of total and gamma' fibrinogen, leading to a 3.6-fold increase in gamma A mRNA, but an 8.3-fold increase in gamma' mRNA.Conclusions: These findings indicate that gamma' fibrinogen is disproportionately up-regulated by inflammatory responses induced by interleukin-6. (C) 2012 Elsevier Ltd. All rights reserved.