...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >Pam3CSK4 Induces MMP-9 Expression in Human Monocytic THP-1 Cells
【24h】

Pam3CSK4 Induces MMP-9 Expression in Human Monocytic THP-1 Cells

机译：Pam3CSK4诱导人类单核细胞THP-1细胞中MMP-9表达。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

>Background: Matrix metalloproteinase (MMP)-9 is known to degrade the extracellular matrix and increased MMP-9 levels are related with the pathogenesis of many inflammatory conditions including obesity. Pam3CSK4 is a synthetic triacylated lipopeptide (LP) which is a potent activator of immune cells and induces cytokine production. However, it is unclear whether Pam3CSK4 is able to induce MMP-9 expression in monocytic cells. We, therefore, determined MMP-9 production by Pam3CSK4-treated THP-1 cells and also investigated the signal transduction pathway(s) involved. Methods: MMP-9 expression was determined by real-time qPCR and ELISA. MMP-9 activity was assessed by zymography. THP-1 cells, THP1-XBlueTM cells, THP1-XBlueTM-defMyD cells, anti-TLR2 mAb and selective pharmacological inhibitors were used to study signaling pathways involved. Phosphorylated and total proteins were detected by western blotting. Results: Pam3CSK4 induced MMP-9 expression (P<0.05) at both mRNA and protein levels in human monocytic THP-1 cells. Increased NF-?oB/AP-1 activity was detected in Pam3CSK4-treated THP-1 cells and MMP-9 production in these cells was significantly suppressed by pre-treatment with anti-TLR2 neutralizing antibody or by inhibition of clathrin-dependent endocytosis. Also, MyD88-/- THP-1 cells did not express MMP-9 following treatment with Pam3CSK4. Inhibition of JNK, MEK/ERK, p38 MAPK and NF-?oB significantly suppressed MMP-9 gene expression (P<0.05). Conclusion: Pam3CSK4 induces MMP-9 production in THP-1 cells through the TLR-2/MyD88-dependent mechanism involving MEK/ERK, JNK, p38 MAPK and NF-?oB/AP-1 activation.
机译：> 背景： 已知基质金属蛋白酶（MMP）-9降解细胞外基质，MMP-9水平升高与包括肥胖在内的许多炎症性疾病的发病机理有关。 Pam3CSK4是合成的三酰基脂肽（LP），是一种有效的免疫细胞激活剂，可诱导细胞因子产生。但是，尚不清楚Pam3CSK4是否能够在单核细胞中诱导MMP-9表达。因此，我们确定了Pam3CSK4处理的THP-1细胞产生的MMP-9，并研究了所涉及的信号转导途径。 方法： 通过实时定量PCR和ELISA检测MMP-9的表达。 MMP-9活性通过酶谱评估。 THP-1细胞，THP1-XBlue TM 细胞，THP1-XBlue TM -defMyD细胞，抗TLR2使用单克隆抗体和选择性药理抑制剂研究涉及的信号通路。通过蛋白质印迹检测磷酸化和总蛋白。 结果： Pam3CSK4诱导人单核THP-1细胞mRNA和蛋白水平的MMP-9表达（P <0.05）。在经Pam3CSK4处理的THP-1细胞中检测到NF-κoB/ AP-1活性增加，并且通过用抗TLR2中和抗体进行预处理或抑制网格蛋白依赖性内吞作用，可显着抑制这些细胞中MMP-9的产生。同样，在用Pam3CSK4处理后，MyD88-/-THP-1细胞不表达MMP-9。抑制JNK，MEK / ERK，p38 MAPK和NF-κB可以显着抑制MMP-9基因的表达（P <0.05）。 结论： Pam3CSK4通过TLR-2 / MyD88依赖性机制（涉及MEK / ERK，JNK，p38 MAPK和NF-？）诱导THP-1细胞中MMP-9的产生。 oB / AP-1激活。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号