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Mediators of Inflammation
Volume 2015, Article ID 964838, 11 pages
http://dx.doi.org/10.1155/2015/964838
Research Article

Oxygen-Loaded Nanodroplets Effectively Abrogate Hypoxia Dysregulating Effects on Secretion of MMP-9 and TIMP-1 by Human Monocytes

1Dipartimento di Oncologia, Università di Torino, 10126 Torino, Italy
2Istituto Nazionale di Ricerca Metrologica (INRIM), 10135 Torino, Italy
3Dipartimento di Neuroscienze, Università di Torino, 10125 Torino, Italy
4Dipartimento di Scienze della Salute, Università di Milano Bicocca, 20900 Monza, Italy
5Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, 10125 Torino, Italy
6Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università di Torino, 10126 Torino, Italy

Received 12 January 2015; Accepted 9 March 2015

Academic Editor: Elzbieta Kolaczkowska

Copyright © 2015 Giulia Rossana Gulino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Monocytes play a key role in the inflammatory stage of the healing process. To allow monocyte migration to injured tissues, the balances between secreted matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) must be finely modulated. However, a reduction of blood supply and local oxygen tension can modify the phenotype of immune cells. Intriguingly, hypoxia might be targeted by new effective oxygenating devices such as 2H,3H-decafluoropentane- (DFP-) based oxygen-loaded nanodroplets (OLNs). Here, hypoxia effects on gelatinase/TIMP release from human peripheral monocytes were investigated, and the therapeutic potential of dextran-shelled OLNs was evaluated. Normoxic monocytes constitutively released ~500 ng/mL MMP-9, ~1.3 ng/mL TIMP-1, and ~0.6 ng/mL TIMP-2 proteins. MMP-2 was not detected. After 24 hours, hypoxia significantly altered MMP-9/TIMP-1 balance by reducing MMP-9 and increasing TIMP-1, without affecting TIMP-2 secretion. Interestingly OLNs, not displaying toxicity to human monocytes after cell internalization, effectively counteracted hypoxia, restoring a normoxia-like MMP-9/TIMP-1 ratio. The action of OLNs was specifically dependent on time-sustained oxygen diffusion up to 24 h from their DFP-based core. Therefore, OLNs appear as innovative, nonconventional, cost-effective, and nontoxic therapeutic tools, to be potentially employed to restore the physiological invasive phenotype of immune cells in hypoxia-associated inflammation.