Matrix metalloproteinase inhibitors prevent the release and proteolytic activity of monocyte/macrophage-derived microparticles.

Authors:
Stefano Fogli
Stefano Fogli
University of Pisa
Tommaso Neri
Tommaso Neri
University of Pisa
Italy
Elisa Nuti
Elisa Nuti
Università di Pisa
Italy
Letizia Mattii
Letizia Mattii
University of Pisa
Pisa | Italy
Caterina Camodeca
Caterina Camodeca
Università di Siena
Italy
Armando Rossello
Armando Rossello
Università degli Studi di Pisa

Pharmacol Rep 2019 Jun 31;71(3):485-490. Epub 2019 Jan 31.

Department of Pharmacy, University of Pisa, Pisa, Italy.

Background: The role of monocyte/macrophage-derived microparticles (MPs) in the pathophysiology of cancer and chronic inflammatory diseases has been reported; nevertheless, the mechanism underlying microparticles release is currently unclear. The aim of the current study was to investigate whether matrix metalloproteinase (MMP) inhibitors could prevent MP shedding from stimulated human monocyte/macrophage.

Methods: Microparticles were obtained by isolated peripheral blood mononuclear cells after stimulation with the calcium ionophore, A23187. MP shedding, intracellular calcium concentration, analysis of RhoA expression, and proteolytic activities of isolated MPs were assessed in the absence or presence of MMP inhibitors.

Results: We demonstrated that MMP inhibitors remarkably prevented MP shedding in a concentration-dependent manner with IC values in the nano- to micromolar range. Such an effect was related to their ability to reduce the intracellular Ca levels induced by the calcium ionophore and the consequent translocation of RhoA from cytosol to membrane. Furthermore, MMP inhibitors could inhibit the proteolytic activity of cell-derived MPs.

Conclusions: The current study provide evidence that MMP inhibitors can prevent MPs shedding from stimulated human monocyte/macrophage and the proteolytic activity of released MPs. Finally, the most active compound tested might represent the lead compound of a new class of molecules with therapeutic potential in cancer and chronic inflammatory diseases.

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Source
http://dx.doi.org/10.1016/j.pharep.2019.01.013DOI Listing
June 2019
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