Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts
Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts
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DOI：
10.1016/j.bbrc.2007.08.003
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发表时间：
2007-10-12
影响因子：
3.1
通讯作者：
Long, Carlin S.
中科院分区：
文献类型：
--
作者：
Brown, R. Dale;Jones, Gayle M.;Long, Carlin S.
我们试图用成年大鼠心脏成纤维细胞来确定细胞因子刺激的基质金属蛋白酶（MMPs）释放与细胞迁移之间的关系。白细胞介素-1 β (IL-1 β)使MMP-2、-3、-9和TIMP-1的释放增加3-6倍，通过免疫印迹和凝胶酶谱测定。肿瘤坏死因子α (TNF α)增强IL-1 β刺激MMP-9的释放，但对MMP-2或-3没有作用。转化生长因子- β 1 （TGF β 1）减弱了对IL-1 β的所有反应。在Boyden室实验中，IL-1 β也是成年大鼠心脏成纤维细胞迁移的最强大刺激。IL-1 β与TNF α联合可显著增强迁移，而TGF β 1则强烈抑制IL-1 β的迁移反应。泛选择性NIMP抑制剂GM 6001有效阻断IL-1 β刺激的迁移。选择性的ERK， JNK和p38 MAP激酶途径的药物抑制剂抑制了单个MMPs的IL-1 β调节。与心肌成纤维细胞迁移相关的NIMP活性增加可能是损伤心肌细胞因子定向重塑的重要决定因素。(C) 2007爱思唯尔公司版权所有。
We sought to define the relationship between cytokine stimulated release of matrix metalloproteinases (MMPs) and cell migration using adult rat cardiac fibroblasts. Interleukin-1 beta (IL-1 beta) increased release of MMP-2, -3, and -9, and TIMP-1, by 3-6-fold, measured by immunoblotting and gel zymography. Tumor necrosis factor-alpha (TNF alpha) augmented IL-1 beta stimulated release of MMP-9, but not MMP-2 or -3. Transforming growth factor-beta 1 (TGF beta 1) attenuated all the responses to IL-1 beta. IL-1 beta was also the most robust stimulus of adult rat cardiac fibroblast migration, measured in Boyden chamber assays. The combination of IL-1 beta plus TNF alpha substantially enhanced migration, whereas TGF beta 1 strongly inhibited the migratory response to IL-1 beta. The pan-selective NIMP inhibitor GM 6001 effectively blocked IL-1 beta stimulated migration. Pharmacologic inhibitors selective for ERK, JNK, and p38 MAP kinase pathways inhibited the IL-1 beta regulation of individual MMPs. Increased NIMP activity associated with migration of cardiac fibroblasts may be important determinants of cytokine-directed remodeling of injured myocardium. (C) 2007 Elsevier Inc. All rights reserved.