Chronic wounds are associated with inflammation, infections, and hypoxic environment. Macrophages play a crucial role in wound healing removing bacteria and secreting signal molecules to coordinate tissue repair. Recently, dextran-shelled Oxygen-Loaded NanoDroplets (OLNDs) have been proposed as new tools to counteract hypoxia in chronic wounds. Here we investigated the effects of OLNDs on Enterococcus faecalis (E. faecalis) killing and the secretion of inflammatory and angiogenic factors by murine (BMDM) and human (dTHP-1, differentiated THP-1) macrophages, in normoxia and hypoxia. Both OLNDs and Oxygen-Free NanoDroplets (OFNDs) signifi-cantly increased reactive oxygen species production by BMDM in normoxia (4.1 and 4 fold increase by 10% OLNDs and OFNDs, respectively, after 120 min) and hypoxia (3.8 and 4 fold increase by 10% OLNDs and OFNDs respectively) but not by dTHP-1. Moreover, only OLNDs induced nitric oxide secretion by BMDM in normoxia. Consequently, both nanodroplets improved E. faecalis killing by BMDM in normoxia (% of killing OLNDs = 44.2%; p < 0.01; OFNDs = 41.4%; p < 0.05) and hypoxia (% of killing OLNDs = 43.1%; p < 0.01; OFNDs = 37.7%; p < 0.05), while dTHP-1-mediated killing was not affected. The secretion of the inflammatory cytokines (TNF alpha, IL-6, IL-1 beta) induced by E. faecalis infection in dTHP-1 was reduced by both types of nanodroplets, sug-gesting a novel anti-inflammatory activity of the dextran shell. Instead, the increase of VEGF induced by hypoxia was reduced only by OLNDs. These data provide new knowledge on the effects of OLNDs as innovative adjuvant in chronic wounds healing promoting bacterial killing and reducing inflammation.

Dextran-shelled oxygen-loaded nanodroplets modulate macrophages killing and inflammatory response to Enterococcus faecalis / F. Perego, R.M. Ticozzi, A. Troia, M. Prato, D. Taramelli, N. Basilico. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 931:(2022 Sep 15), pp. 175161.1-175161.10. [10.1016/j.ejphar.2022.175161]

Dextran-shelled oxygen-loaded nanodroplets modulate macrophages killing and inflammatory response to Enterococcus faecalis

F. Perego
Primo
;
R.M. Ticozzi
Secondo
;
D. Taramelli
Penultimo
;
N. Basilico
Ultimo
2022

Abstract

Chronic wounds are associated with inflammation, infections, and hypoxic environment. Macrophages play a crucial role in wound healing removing bacteria and secreting signal molecules to coordinate tissue repair. Recently, dextran-shelled Oxygen-Loaded NanoDroplets (OLNDs) have been proposed as new tools to counteract hypoxia in chronic wounds. Here we investigated the effects of OLNDs on Enterococcus faecalis (E. faecalis) killing and the secretion of inflammatory and angiogenic factors by murine (BMDM) and human (dTHP-1, differentiated THP-1) macrophages, in normoxia and hypoxia. Both OLNDs and Oxygen-Free NanoDroplets (OFNDs) signifi-cantly increased reactive oxygen species production by BMDM in normoxia (4.1 and 4 fold increase by 10% OLNDs and OFNDs, respectively, after 120 min) and hypoxia (3.8 and 4 fold increase by 10% OLNDs and OFNDs respectively) but not by dTHP-1. Moreover, only OLNDs induced nitric oxide secretion by BMDM in normoxia. Consequently, both nanodroplets improved E. faecalis killing by BMDM in normoxia (% of killing OLNDs = 44.2%; p < 0.01; OFNDs = 41.4%; p < 0.05) and hypoxia (% of killing OLNDs = 43.1%; p < 0.01; OFNDs = 37.7%; p < 0.05), while dTHP-1-mediated killing was not affected. The secretion of the inflammatory cytokines (TNF alpha, IL-6, IL-1 beta) induced by E. faecalis infection in dTHP-1 was reduced by both types of nanodroplets, sug-gesting a novel anti-inflammatory activity of the dextran shell. Instead, the increase of VEGF induced by hypoxia was reduced only by OLNDs. These data provide new knowledge on the effects of OLNDs as innovative adjuvant in chronic wounds healing promoting bacterial killing and reducing inflammation.
No
English
Enterococcus faecalis; Inflammation; Macrophages; Nanodroplets; Oxygen; Wound
Settore MED/04 - Patologia Generale
Articolo
Esperti anonimi
Pubblicazione scientifica
   Hypoxia and chronic wounds in the elderly: a multidisciplinary approach from pathogenetic mechanisms to nonconventional nanotherapies
   HyWoNNa
   FONDAZIONE CARIPLO
   2015-0550
15-set-2022
Elsevier
931
175161
1
10
10
Pubblicato
Periodico con rilevanza internazionale
pubmed
scopus
crossref
wos
Aderisco
info:eu-repo/semantics/article
Dextran-shelled oxygen-loaded nanodroplets modulate macrophages killing and inflammatory response to Enterococcus faecalis / F. Perego, R.M. Ticozzi, A. Troia, M. Prato, D. Taramelli, N. Basilico. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 931:(2022 Sep 15), pp. 175161.1-175161.10. [10.1016/j.ejphar.2022.175161]
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Prodotti della ricerca::01 - Articolo su periodico
6
262
Article (author)
Periodico con Impact Factor
F. Perego, R.M. Ticozzi, A. Troia, M. Prato, D. Taramelli, N. Basilico
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/952697
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