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The Role of Urokinase, Tumor Necrosis Factor, and Matrix Metalloproteinase-9 in Monocyte Activation

  • M. Yu. MenshikovEmail author
  • I. S. Stafeev
  • E. S. Zubkova
  • I. B. Beloglazova
  • E. I. Ratner
  • K. V. Dergilev
  • E. V. Parfyonova
Article
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TNFα mediates the expression of MMP-9 in THP-1 monocytes induced by urokinase (uPA). Upregulation of MMP-9 caused by uPA and TNFα is suppressed by etanercept, a TNFα inhibitor. In addition, uPA stimulates TNFα mRNA expression. Both uPA and TNFα induce ROS generation in monocytes, while MMP-9 secretion induced by uPA and TNFα is inhibited by antioxidants. Inhibitors of NFκB, ligands of PPARα and PPARγ receptors, and SIRT1 activators negatively affect MMP-9 secretion induced by uPA. MMP-9 secretion during monocyte differentiation into macrophages is downregulated by etanercept and antioxidants. These factors as well as MMP inhibitor GM6001 reduce the number of macrophages attached to substrate during cell differentiation, indicating the role of urokinase, TNFα, and ROS in MMP expression in monocytes and MMP involvement in macrophage maturation.

Key words

monocyte macrophage urokinase tumor necrosis factor matrix metalloproteinase 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • M. Yu. Menshikov
    • 1
    Email author
  • I. S. Stafeev
    • 1
  • E. S. Zubkova
    • 1
  • I. B. Beloglazova
    • 1
  • E. I. Ratner
    • 1
  • K. V. Dergilev
    • 1
  • E. V. Parfyonova
    • 1
  1. 1.National Research Center for CardiologyHealth Ministry of Russian FederationMoscowRussia

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