C-Reactive Protein Stimulates MMP-1 Expression in U937 Histiocytes Through Fc&ggr;RII and Extracellular Signal-Regulated Kinase Pathway:: An Implication of CRP Involvement in Plaque Destabilization
C-Reactive Protein Stimulates MMP-1 Expression in U937 Histiocytes Through Fc&ggr;RII and Extracellular Signal-Regulated Kinase Pathway:: An Implication of CRP Involvement in Plaque Destabilization
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C 反应蛋白通过 Fc 刺激 U937 组织细胞中 MMP-1 的表达
DOI：
10.1161/01.atv.0000104014.24367.16
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Yan Huang
中科院分区：
文献类型：
--
作者：
Takeyla N Williams;Cecelia Zhang;B. A. Game;Lin He;Yan Huang
目的——已证明血浆 C 反应蛋白 (CRP) 水平是急性冠状动脉综合征的独立预测因子，并且与斑块减弱相关。然而，其根本机制尚不清楚。在这项研究中，我们研究了 CRP 对基质金属蛋白酶-1 (MMP-1) 表达的影响，该表达与人类 U937 组织细胞和单核细胞来源的巨噬细胞的斑块脆弱性有关。方法和结果——条件培养基中 MMP-1 的酶联免疫吸附测定表明，用 100 µg/mL CRP 处理 U937 细胞 24 小时，导致 MMP-1 分泌增加 3 至 5 倍。 CRP 还显着刺激人单核细胞来源的巨噬细胞释放 MMP-1。相反，CRP 对金属蛋白酶组织抑制剂 1 (TIMP-1) 的分泌没有影响。 Northern印迹显示CRP上调MMP-1 mRNA表达。胶原酶活性测定表明，CRP 增加了细胞条件培养基中胶原蛋白的降解活性。此外，结果表明，CRP 对 MMP-1 分泌的刺激被抗 CD32 抑制，但不被抗 CD64 抗体和丝裂原激活蛋白激酶/细胞外信号调节激酶 (MEK) 抑制剂 PD98059 抑制。最后，Western blot显示CRP刺激细胞外信号调节激酶的磷酸化。结论—本研究表明 CRP 通过 Fc&ggr;RII 和细胞外信号调节激酶途径刺激 U937 细胞表达 MMP-1。这些发现表明，CRP 可能促进基质降解，从而导致斑块脆弱性。
Objective—It has been shown that plasma level of C-reactive protein (CRP) is an independent predictor for acute coronary syndromes and is associated with plaque weakening. However, the underlying mechanisms are not well understood. In this study, we investigated the effect of CRP on the expression of matrix metalloproteinase-1 (MMP-1) that has been implicated in plaque vulnerability by human U937 histiocytes and monocyte-derived macrophages. Methods and Results—Enzyme-linked immunosorbent assay of MMP-1 in conditioned medium showed that treatment of U937 cells with 100 &mgr;g/mL of CRP for 24 hour led to a 3- to 5-fold increase in MMP-1 secretion. CRP also markedly stimulated MMP-1 release from human monocyte-derived macrophages. In contrast, CRP had no effect on tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion. Northern blot showed that CRP upregulated MMP-1 mRNA expression. Collagenase activity assay showed that CRP increased collagen-degrading activity in cell-conditioned medium. Furthermore, results showed that the stimulation of MMP-1 secretion by CRP was inhibited by anti-CD32, but not by anti-CD64 antibody, and by mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor PD98059. Finally, Western blot showed that CRP stimulated phosphorylation of extracellular signal-regulated kinase. Conclusions—This study demonstrates that CRP stimulates MMP-1 expression by U937 cells through Fc&ggr;RII and extracellular signal-regulated kinase pathway. These findings suggest that CRP may promote matrix degradation and thus contribute to plaque vulnerability.
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影响因子：
20.1
作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
20.3
作者：
J. Cermak;N. S. Key;R. R. Bach-R.;J. Balla;H. S. Jacob;G. Vercellotti
通讯作者：
J. Cermak;N. S. Key;R. R. Bach-R.;J. Balla;H. S. Jacob;G. Vercellotti
DOI：
10.1016/s0735-1097(01)01804-6
发表时间：
2002-02-20
影响因子：
24
作者：
Zebrack, JS;Muhlestein, JB;Anderson, JL
通讯作者：
Anderson, JL
影响因子：
15.9
作者：
Stein, MP;Edberg, JC;Du Clos, TW
通讯作者：
Du Clos, TW
影响因子：
37.8
作者：
Aikawa, M;Rabkin, E;Libby, P
通讯作者：
Libby, P