The Role of Urokinase, Tumor Necrosis Factor, and Matrix Metalloproteinase-9 in Monocyte Activation
- Authors: Menshikov M.Y.1, Stafeev I.S.1, Zubkova E.S.1, Beloglazova I.B.1, Ratner E.I.1, Dergilev K.V.1, Parfyonova E.V.1
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Affiliations:
- National Research Center for Cardiology, Health Ministry of Russian Federation
- Issue: Vol 167, No 4 (2019)
- Pages: 492-495
- Section: Article
- URL: https://journals.rcsi.science/0007-4888/article/view/241817
- DOI: https://doi.org/10.1007/s10517-019-04557-2
- ID: 241817
Cite item
Abstract
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.
About the authors
M. Yu. Menshikov
National Research Center for Cardiology, Health Ministry of Russian Federation
Author for correspondence.
Email: myumensh@mail.ru
Russian Federation, Moscow
I. S. Stafeev
National Research Center for Cardiology, Health Ministry of Russian Federation
Email: myumensh@mail.ru
Russian Federation, Moscow
E. S. Zubkova
National Research Center for Cardiology, Health Ministry of Russian Federation
Email: myumensh@mail.ru
Russian Federation, Moscow
I. B. Beloglazova
National Research Center for Cardiology, Health Ministry of Russian Federation
Email: myumensh@mail.ru
Russian Federation, Moscow
E. I. Ratner
National Research Center for Cardiology, Health Ministry of Russian Federation
Email: myumensh@mail.ru
Russian Federation, Moscow
K. V. Dergilev
National Research Center for Cardiology, Health Ministry of Russian Federation
Email: myumensh@mail.ru
Russian Federation, Moscow
E. V. Parfyonova
National Research Center for Cardiology, Health Ministry of Russian Federation
Email: myumensh@mail.ru
Russian Federation, Moscow