Skip to main content
SpringerLink
Log in

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

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abraham E, Gyetko MR, Kuhn K, Arcaroli J, Strassheim D, Park JS, Shetty S, Idell S. Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation. J. Immunol. 2003;170(11):5644-5651.

    Article  CAS  Google Scholar 

  2. Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R. Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor. Med. Oncol. 2014;31(1):774.

    Article  CAS  Google Scholar 

  3. Heidinger M, Kolb H, Krell HW, Jochum M, Ries C. Modulation of autocrine TNF-alpha-stimulated matrix metalloproteinase 9 (MMP-9) expression by mitogen-activated protein kinases in THP-1 monocytic cells. Biol. Chem. 2006;387(1):69-78.

    Article  CAS  Google Scholar 

  4. Jamaluddin M, Wang S, Boldogh I, Tian B, Brasier AR. TNFalpha-induced NF-kappaB/RelA Ser(276) phosphorylation and enhanceosome formation is mediated by an ROS-dependent PKAc pathway. Cell. Signal. 2007;19(7):1419-1433.

    Article  CAS  Google Scholar 

  5. Kohro T, Tanaka T, Murakami T, Wada Y, Aburatani H, Hamakubo T, Kodama T. A comparison of differences in the gene expression profiles of phorbol 12-myristate 13-acetate differentiated THP-1 cells and human monocyte-derived macrophage. J. Atheroscler. Thromb. 2004;11(2):88-97.

    Article  CAS  Google Scholar 

  6. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J. Immunol. 2006;177(10):7303-7311.

    Article  CAS  Google Scholar 

  7. Menshikov M, Torosyan N, Elizarova E, Plakida K, Vorotnikov A, Parfyonova Y, Stepanova V, Bobik A, Berk B, Tkachuk V. Urokinase induces matrix metalloproteinase-9/gelatinase B expression in THP-1 monocytes via ERK1/2 and cytosolic phospholipase A2 activation and eicosanoid production. J. Vasc. Res. 2006;43(5):482-490.

    Article  CAS  Google Scholar 

  8. Murdaca G, Colombo BM, Puppo F. Anti-TNF-alpha inhibitors: a new therapeutic approach for inflammatory immunemediated diseases: an update upon efficacy and adverse events. Int. J. Immunopathol. Pharmacol. 2009;22(3):557-565.

    Article  CAS  Google Scholar 

  9. Paland N, Aharoni S, Fuhrman B. Urokinase-type plasminogen activator (uPA) modulates monocyte-to-macrophage differentiation and prevents Ox-LDL-induced macrophage apoptosis. Atherosclerosis. 2013;231(1):29-38.

    Article  CAS  Google Scholar 

  10. Reichel CA, Kanse SM, Krombach F. At the interface of fibrinolysis and inflammation: the role of urokinase-type plasminogen activator in the leukocyte extravasation cascade. Trends Cardiovasc. Med. 2012;22(7):192-196.

    Article  CAS  Google Scholar 

  11. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J. Cell. Mol. Med. 2005;9(2):267-285.

    Article  CAS  Google Scholar 

  12. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 2012;122(3):787-795.

    Article  CAS  Google Scholar 

  13. Stacey KJ, Fowles LF, Colman MS, Ostrowski MC, Hume DA. Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor. Mol. Cell. Biol. 1995;15(6):3430-3441.

    Article  CAS  Google Scholar 

  14. Webster NL, Crowe SM. Matrix metalloproteinases, their production by monocytes and macrophages and their potential role in HIV-related diseases. J. Leukoc. Biol. 2006;80(5):1052-1066.

    Article  CAS  Google Scholar 

  15. Zajac E, Schweighofer B, Kupriyanova TA, Juncker-Jensen A, Minder P, Quigley JP, Deryugina EI. Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9. Blood. 2013;122(25):4054-4067.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Research Center for Cardiology, Health Ministry of Russian Federation, Moscow, Russia

    M. Yu. Menshikov, I. S. Stafeev, E. S. Zubkova, I. B. Beloglazova, E. I. Ratner, K. V. Dergilev & E. V. Parfyonova

Authors
  1. M. Yu. Menshikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. S. Stafeev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. S. Zubkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. B. Beloglazova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. I. Ratner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. V. Dergilev
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. V. Parfyonova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Yu. Menshikov.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 4, pp. 478-482, April, 2019

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Menshikov, M.Y., Stafeev, I.S., Zubkova, E.S. et al. The Role of Urokinase, Tumor Necrosis Factor, and Matrix Metalloproteinase-9 in Monocyte Activation. Bull Exp Biol Med 167, 492–495 (2019). https://doi.org/10.1007/s10517-019-04557-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-019-04557-2

Key words

Search

Navigation