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.

Gulino, G., Magnetto, C., Khadjavi, A., PANARITI, A., RIVOLTA, I., Soster, M., et al. (2015). Oxygen-loaded nanodroplets effectively abrogate hypoxia dysregulating effects on secretion of MMP-9 and TIMP-1 by human monocytes. MEDIATORS OF INFLAMMATION, 2015, 11 [10.1155/2015/964838].

Oxygen-loaded nanodroplets effectively abrogate hypoxia dysregulating effects on secretion of MMP-9 and TIMP-1 by human monocytes

PANARITI, ALICE LUCIA;RIVOLTA, ILARIA;
2015

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.
Articolo in rivista - Articolo scientifico
Cell Survival; Humans; Hypoxia; Matrix Metalloproteinase 9; Monocytes; Nanoparticles; Oxygen; Tissue Inhibitor of Metalloproteinase-1; Immunology; Cell Biology
English
11
Gulino, G., Magnetto, C., Khadjavi, A., PANARITI, A., RIVOLTA, I., Soster, M., et al. (2015). Oxygen-loaded nanodroplets effectively abrogate hypoxia dysregulating effects on secretion of MMP-9 and TIMP-1 by human monocytes. MEDIATORS OF INFLAMMATION, 2015, 11 [10.1155/2015/964838].
Gulino, G; Magnetto, C; Khadjavi, A; Panariti, A; Rivolta, I; Soster, M; Argenziano, M; Cavalli, R; Giribaldi, G; Guiot, C; Prato, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/141736
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